首页 > 最新文献

Cancer Immunology, Immunotherapy最新文献

英文 中文
Triple therapy boosts survival in NSCLC patients with brain metastases: a retrospective cohort study of chemotherapy, ICIs, and antiangiogenic agents. 三联疗法提高了脑转移 NSCLC 患者的生存率:化疗、ICIs 和抗血管生成药物的回顾性队列研究。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-06 DOI: 10.1007/s00262-024-03797-0
Dingyi Yang, Erha Munai, Siwei Zeng, Dan Tao, Ze Yuan, Liang Du, Wei Zhou, Yongzhong Wu, Xiao-Dong Zhu
<p><strong>Background: </strong>Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood-brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during brain metastasis to radiotherapy evaluation window in improving patient survival.</p><p><strong>Methods: </strong>In this retrospective cohort study, we evaluated 209 NSCLC patients with non-sensitive mutations and BMs, treated between 2016 and 2023 at two tertiary medical centers (Chongqing University Cancer Hospital and Guangxi Medical University Cancer Hospital). The patients were divided into three groups, namely chemotherapy alone (C; n = 95), chemotherapy plus immune checkpoint inhibitors (ICIs) (C + I; n = 62), and chemotherapy with ICIs and antiangiogenic therapy (A) (C + I + A; n = 52). Statistical analyses were performed using R software, version 4.3.3. Categorical variables were compared using Fisher's exact test, and survival curves were estimated with the Kaplan-Meier method and compared via the log-rank test. Univariate and multivariate Cox regression models were used to assess factors associated with overall survival (OS). Bayesian model averaging (BMA) was employed to address model uncertainty and improve result robustness. Subgroup analyses evaluated treatment-related mortality risk.</p><p><strong>Results: </strong>From an initial cohort of 658 NSCLC patients with BMs, 209 were analyzed with a median age of 59; the majority were male (80.9%) and diagnosed with adenocarcinoma (78.9%). Univariate analysis identified significant variables influencing outcomes, including BMs radiotherapy EQD2, BMs count, local thoracic treatment, BMs radiotherapy field, intracranial response, and systemic treatment post-BMs diagnosis. The C + I + A regimen significantly improved median OS to 23.6 months compared to 11.4 months with C and 16.2 months with C + I, with a hazard ratio (HR) of 0.60 (95% CI: 0.43-0.82; P < 0.0001). The two-year OS rate was highest in the C + I + A group at 38.5%, versus 10.5% in C and 20.4% in C + I (P < 0.001). Cox regression and BMA analyses confirmed the stability of BMA in providing HR estimates, yielding area under the curve (AUC) values of 0.785 for BMA and 0.793 for the Cox model, with no significant difference in predictive performance. Subgroup analysis revealed a 71% mortality risk reduction with C + I + A (HR: 0.29; 95% CI: 0.18-0.47; P < 0.0001), showing consistent benefits regardless of patient sex, BMs count, extracranial metastases presence, and local thoracic treatments. Treatment sequence analysis indicated a median OS of 33.4 months for patients starting with A, though not statistically significant (HR: 0.59; P = 0.36). The overall incidence of radiation-induced brain injury was low at 3.3%, with rates in the C, C + I, and C + I + A groups being 3.2%, 4.8%, and 1.9%, respectively (P = 0.
背景:非小细胞肺癌(NSCLC)患者脑转移(BMs)的治疗,尤其是那些基因突变不敏感的患者,由于药物通过血脑屏障(BBB)的能力有限而受到阻碍。这项回顾性研究探讨了脑转移至放疗评估窗口期间的全身治疗在提高患者生存率方面的疗效:在这项回顾性队列研究中,我们评估了2016年至2023年间在两家三级医疗中心(重庆大学附属肿瘤医院和广西医科大学附属肿瘤医院)接受治疗的209例非敏感突变和脑转移的NSCLC患者。患者被分为三组,即单纯化疗组(C;n = 95)、化疗加免疫检查点抑制剂(ICIs)组(C + I;n = 62)和化疗加ICIs和抗血管生成治疗组(A)(C + I + A;n = 52)。统计分析使用 4.3.3 版 R 软件进行。分类变量的比较采用费舍尔精确检验,生存曲线的估计采用卡普兰-梅耶法,并通过对数秩检验进行比较。单变量和多变量考克斯回归模型用于评估与总生存率(OS)相关的因素。采用贝叶斯模型平均法(BMA)来解决模型的不确定性并提高结果的稳健性。亚组分析评估了与治疗相关的死亡率风险:在658名患有BMs的NSCLC患者的初始队列中,分析了209名患者,中位年龄为59岁;大多数患者为男性(80.9%),诊断为腺癌(78.9%)。单变量分析确定了影响预后的重要变量,包括BMs放疗EQD2、BMs数量、局部胸部治疗、BMs放疗野、颅内反应以及BMs确诊后的全身治疗。与C+I+A方案的11.4个月和C+I方案的16.2个月相比,C+I+A方案的中位OS显著提高至23.6个月,危险比(HR)为0.60(95% CI:0.43-0.82;P 结论:我们的研究表明,C+I+A方案的中位OS显著提高:我们的研究表明,C+I+A联合疗法在改善非敏感基因突变BM的NSCLC患者的OS和降低死亡风险方面具有显著疗效。依次给予 A 后再给予 ICIs 与颅脑放疗显示出良好的协同效应,凸显了优化治疗顺序的潜力。这些发现强调了定制化联合疗法在复杂肿瘤治疗中的疗效,并表明我们的方法可以显著改善这一具有挑战性的患者群体的临床疗效。
{"title":"Triple therapy boosts survival in NSCLC patients with brain metastases: a retrospective cohort study of chemotherapy, ICIs, and antiangiogenic agents.","authors":"Dingyi Yang, Erha Munai, Siwei Zeng, Dan Tao, Ze Yuan, Liang Du, Wei Zhou, Yongzhong Wu, Xiao-Dong Zhu","doi":"10.1007/s00262-024-03797-0","DOIUrl":"10.1007/s00262-024-03797-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Treatment of brain metastases (BMs) in non-small cell lung cancer (NSCLC) patients, especially those with non-sensitive genetic mutations, is hindered by limited drug delivery through the blood-brain barrier (BBB). This retrospective study explores the efficacy of systemic treatments during brain metastasis to radiotherapy evaluation window in improving patient survival.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this retrospective cohort study, we evaluated 209 NSCLC patients with non-sensitive mutations and BMs, treated between 2016 and 2023 at two tertiary medical centers (Chongqing University Cancer Hospital and Guangxi Medical University Cancer Hospital). The patients were divided into three groups, namely chemotherapy alone (C; n = 95), chemotherapy plus immune checkpoint inhibitors (ICIs) (C + I; n = 62), and chemotherapy with ICIs and antiangiogenic therapy (A) (C + I + A; n = 52). Statistical analyses were performed using R software, version 4.3.3. Categorical variables were compared using Fisher's exact test, and survival curves were estimated with the Kaplan-Meier method and compared via the log-rank test. Univariate and multivariate Cox regression models were used to assess factors associated with overall survival (OS). Bayesian model averaging (BMA) was employed to address model uncertainty and improve result robustness. Subgroup analyses evaluated treatment-related mortality risk.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From an initial cohort of 658 NSCLC patients with BMs, 209 were analyzed with a median age of 59; the majority were male (80.9%) and diagnosed with adenocarcinoma (78.9%). Univariate analysis identified significant variables influencing outcomes, including BMs radiotherapy EQD2, BMs count, local thoracic treatment, BMs radiotherapy field, intracranial response, and systemic treatment post-BMs diagnosis. The C + I + A regimen significantly improved median OS to 23.6 months compared to 11.4 months with C and 16.2 months with C + I, with a hazard ratio (HR) of 0.60 (95% CI: 0.43-0.82; P &lt; 0.0001). The two-year OS rate was highest in the C + I + A group at 38.5%, versus 10.5% in C and 20.4% in C + I (P &lt; 0.001). Cox regression and BMA analyses confirmed the stability of BMA in providing HR estimates, yielding area under the curve (AUC) values of 0.785 for BMA and 0.793 for the Cox model, with no significant difference in predictive performance. Subgroup analysis revealed a 71% mortality risk reduction with C + I + A (HR: 0.29; 95% CI: 0.18-0.47; P &lt; 0.0001), showing consistent benefits regardless of patient sex, BMs count, extracranial metastases presence, and local thoracic treatments. Treatment sequence analysis indicated a median OS of 33.4 months for patients starting with A, though not statistically significant (HR: 0.59; P = 0.36). The overall incidence of radiation-induced brain injury was low at 3.3%, with rates in the C, C + I, and C + I + A groups being 3.2%, 4.8%, and 1.9%, respectively (P = 0.","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A comprehensive and longitudinal evaluation of the different populations of lymphoid and myeloid cells in the peripheral blood of patients treated with chemoradiotherapy for head and neck cancer. 对头颈部癌症化疗患者外周血中不同的淋巴细胞和骨髓细胞群进行全面和纵向评估。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03810-6
Jens von der Grün, Martina Broglie, Matthias Guckenberger, Panagiotis Balermpas

Background: Immunotherapy provided significant survival benefits for recurrent and metastatic patients with head and neck cancer. These improvements could not be reproduced in patients treated with curative-intent chemoradiotherapy (CRT) and the optimal radio-immunotherapy (RIT) concepts have yet to be designed. Exploration and analysis of the pre-therapeutic immune status of these patients and the changes occurring during the treatment course could be crucial in rationally designing future combined treatments.

Methods: Blood samples were collected from a cohort of 25 head and neck cancer patients treated with curative-intended (C)-RT prior to therapy, after the first week of treatment, and three months after treatment completion. Peripheral blood mononuclear cells (PBMCs) or all nucleated blood cells were isolated and analyzed via flow cytometry.

Results: At baseline, patients showed reduced monocyte and lymphocyte counts compared to healthy individuals. Although overall CD8+ T-cell frequencies were reduced, the proportion of memory subsets were increased in patients. Radiotherapy (RT) treatment led to a further increase in CD8+ effector memory T-cells. Among myeloid populations, tumor-promoting subsets became less abundant after RT, in favor of pro-inflammatory cells.

Conclusion: The present study prospectively demonstrated a complex interplay and distinct longitudinal changes in the composition of lymphocytic and myeloid populations during curative (C)-RT of head and neck cancer. Further validation of this method in a larger cohort could allow for better treatment guidance and tailored incorporation of immunotherapies (IT) in the future.

背景:免疫疗法为复发和转移性头颈癌患者带来了明显的生存益处。这些改善无法在接受治愈性放化疗(CRT)的患者身上重现,最佳的放射免疫疗法(RIT)概念仍有待设计。探索和分析这些患者治疗前的免疫状态以及治疗过程中发生的变化,对于合理设计未来的联合疗法至关重要:方法:在治疗前、治疗第一周后和治疗结束三个月后,从25名接受治疗性意向(C)-RT治疗的头颈部癌症患者中采集血液样本。外周血单核细胞(PBMC)或所有有核血细胞被分离出来,并通过流式细胞术进行分析:结果:与健康人相比,基线期患者的单核细胞和淋巴细胞数量减少。虽然患者体内 CD8+ T 细胞的总体频率降低了,但记忆亚群的比例却增加了。放疗(RT)治疗使CD8+效应记忆T细胞进一步增加。在骨髓细胞群中,RT治疗后肿瘤促进亚群的数量减少,而有利于炎症细胞:本研究前瞻性地展示了头颈部癌症根治性(C)RT期间淋巴细胞和髓系细胞群组成的复杂相互作用和明显纵向变化。在更大的群体中进一步验证这种方法,可在未来提供更好的治疗指导并有针对性地纳入免疫疗法(IT)。
{"title":"A comprehensive and longitudinal evaluation of the different populations of lymphoid and myeloid cells in the peripheral blood of patients treated with chemoradiotherapy for head and neck cancer.","authors":"Jens von der Grün, Martina Broglie, Matthias Guckenberger, Panagiotis Balermpas","doi":"10.1007/s00262-024-03810-6","DOIUrl":"10.1007/s00262-024-03810-6","url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy provided significant survival benefits for recurrent and metastatic patients with head and neck cancer. These improvements could not be reproduced in patients treated with curative-intent chemoradiotherapy (CRT) and the optimal radio-immunotherapy (RIT) concepts have yet to be designed. Exploration and analysis of the pre-therapeutic immune status of these patients and the changes occurring during the treatment course could be crucial in rationally designing future combined treatments.</p><p><strong>Methods: </strong>Blood samples were collected from a cohort of 25 head and neck cancer patients treated with curative-intended (C)-RT prior to therapy, after the first week of treatment, and three months after treatment completion. Peripheral blood mononuclear cells (PBMCs) or all nucleated blood cells were isolated and analyzed via flow cytometry.</p><p><strong>Results: </strong>At baseline, patients showed reduced monocyte and lymphocyte counts compared to healthy individuals. Although overall CD8<sup>+</sup> T-cell frequencies were reduced, the proportion of memory subsets were increased in patients. Radiotherapy (RT) treatment led to a further increase in CD8<sup>+</sup> effector memory T-cells. Among myeloid populations, tumor-promoting subsets became less abundant after RT, in favor of pro-inflammatory cells.</p><p><strong>Conclusion: </strong>The present study prospectively demonstrated a complex interplay and distinct longitudinal changes in the composition of lymphocytic and myeloid populations during curative (C)-RT of head and neck cancer. Further validation of this method in a larger cohort could allow for better treatment guidance and tailored incorporation of immunotherapies (IT) in the future.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration. 杜伐单抗加化疗治疗晚期胆管癌的疗效及生物标志物探索。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03796-1
Yunxin Lu, Yin Jin, Furong Liu, Zixian Wang, Wen Zhou, Yang Zhang, Bing Bai, Yun Wang, Zhiqiang Wang, Man Nie, Huiyan Luo, Xiaoli Wei, Chuqiao Liang, Guifang Guo, Miaozhen Qiu, Jianwen Chen, Yu Liu, Shengping Li, Yuhong Li, Fenghua Wang, Feng Wang, Peidong Chi, Dongsheng Zhang

Background: The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.

Methods: ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.

Results: A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.

Conclusion: This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.

背景:抗PD-L1抗体durvalumab已被批准用于一线晚期胆管癌(ABC)。迄今为止,尚缺乏预测疗效的生物标志物:方法:回顾性入组接受吉西他滨为基础的化疗并使用或不使用durvalumab的ABC患者,并从病历中检索他们的基线临床病理指标。计算并分析总生存期(OS)和无进展生存期(PFS)。使用酶联免疫吸附试验等检测试剂盒检测了 48 例患者的外周生物标志物水平。通过靶向新一代测序描绘了可获得肿瘤组织的27名患者的基因组变化:2020年1月至2022年12月期间,共有186名符合纳入标准的ABC患者最终被纳入本研究。其中,93名患者接受了杜瓦鲁单抗联合化疗,其余患者接受了单独化疗。与单独化疗相比,Durvalumab联合化疗可显著改善既往未接受过治疗的ABC患者的PFS(6.77个月 vs. 4.99个月;危险比0.65 [95% CI 0.48-0.88];P = 0.005),但OS(14.29个月 vs. 13.24个月;危险比0.91 [95% CI 0.62-1.32];P = 0.608)却没有改善。接受化疗和不接受杜伐单抗治疗的患者的客观反应率(ORR)分别为19.1%和7.8%。治疗前的sPD-L1、CSF1R和OPG被确定为接受度伐卢单抗治疗患者的重要预后预测因子。ADGRB3和RNF43突变在对化疗加杜瓦鲁单抗有反应的患者中富集,并与较好的生存期相关:这项回顾性真实世界研究证实,在治疗无效的ABC患者中,度瓦鲁单抗联合化疗可带来临床获益。外周sPD-L1和CSF1R是这一治疗策略很有希望的预后生物标志物。ADGRB3或RNF43突变的存在可改善免疫治疗结果的分层,但仍需进一步研究以探索其潜在机制。
{"title":"Efficacy of durvalumab plus chemotherapy in advanced biliary duct cancer and biomarkers exploration.","authors":"Yunxin Lu, Yin Jin, Furong Liu, Zixian Wang, Wen Zhou, Yang Zhang, Bing Bai, Yun Wang, Zhiqiang Wang, Man Nie, Huiyan Luo, Xiaoli Wei, Chuqiao Liang, Guifang Guo, Miaozhen Qiu, Jianwen Chen, Yu Liu, Shengping Li, Yuhong Li, Fenghua Wang, Feng Wang, Peidong Chi, Dongsheng Zhang","doi":"10.1007/s00262-024-03796-1","DOIUrl":"10.1007/s00262-024-03796-1","url":null,"abstract":"<p><strong>Background: </strong>The anti-PD-L1 antibody durvalumab has been approved for use in first-line advanced biliary duct cancer (ABC). So far, predictive biomarkers of efficacy are lacking.</p><p><strong>Methods: </strong>ABC patients who underwent gemcitabine-based chemotherapy with or without durvalumab were retrospectively enrolled, and their baseline clinical pathological indices were retrieved from medical records. Overall (OS) and progression free survival (PFS) were calculated and analyzed. The levels of peripheral biomarkers from 48 patients were detected with assay kits including enzyme-linked immunosorbent assay. Genomic alterations in 27 patients whose tumor tissues were available were depicted via targeted next-generation sequencing.</p><p><strong>Results: </strong>A total of 186 ABC patients met the inclusion criteria between January 2020 and December 2022 were finally enrolled in this study. Of these, 93 patients received chemotherapy with durvalumab and the rest received chemotherapy alone. Durvalumab plus chemotherapy demonstrated significant improvements in PFS (6.77 vs. 4.99 months; hazard ratio 0.65 [95% CI 0.48-0.88]; P = 0.005), but not OS (14.29 vs. 13.24 months; hazard ratio 0.91 [95% CI 0.62-1.32]; P = 0.608) vs. chemotherapy alone in previously untreated ABC patients. The objective response rate (ORR) in patients receiving chemotherapy with and without durvalumab was 19.1% and 7.8%, respectively. Pretreatment sPD-L1, CSF1R and OPG were identified as significant prognosis predictors in patients receiving durvalumab. ADGRB3 and RNF43 mutations were enriched in patients who responded to chemotherapy plus durvalumab and correlated with superior survival.</p><p><strong>Conclusion: </strong>This retrospective real-world study confirmed the clinical benefit of durvalumab plus chemotherapy in treatment-naïve ABC patients. Peripheral sPD-L1 and CSF1R are promising prognostic biomarkers for this therapeutic strategy. Presence of ADGRB3 or RNF43 mutations could improve the stratification of immunotherapy outcomes, but further studies are warranted to explore the underlying mechanisms.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Outcome of immune checkpoint inhibitor treatment in non-small cell lung cancer patients with interstitial lung abnormalities: clinical utility of subcategorizing interstitial lung abnormalities. 肺间质异常的非小细胞肺癌患者接受免疫检查点抑制剂治疗的结果:肺间质异常亚分类的临床实用性。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03792-5
Ryota Kikuchi, Yusuke Watanabe, Takashi Okuma, Hiroyuki Nakamura, Shinji Abe

Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90-10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62-17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs.

肺间质异常(ILAs)是免疫检查点抑制剂(ICI)相关肺炎(ICI-P)的危险因素。然而,非小细胞肺癌(NSCLC)患者的影像学模式与免疫治疗结果和治疗策略之间的关系仍不清楚。我们对接受 ICI 治疗的 ILAs 合并 NSCLC 患者进行了回顾性评估。根据弗莱施纳协会 2020 年的立场文件,ILAs 被细分为非胸膜下、胸膜下非纤维化和胸膜下纤维化(SF)。我们调查了ICI-P的发病率、ICI-P的风险因素、肺癌预后以及ILAs的放射学进展。在481名接受过ICI治疗的患者中,79人(16.4%)患有ILAs(45名非SF患者和34名SF患者)。SF-ILA患者的ICI-P累积发生率(危险比,4.57;95%置信区间[CI],1.90-10.98;P = 0.001)以及任何等级和等级≥3的ICI-P发生率均高于非SF-ILA患者(所有等级:7/45 [15.6%)] vs. 18/34 [52.9%];P = 0.001)。
{"title":"Outcome of immune checkpoint inhibitor treatment in non-small cell lung cancer patients with interstitial lung abnormalities: clinical utility of subcategorizing interstitial lung abnormalities.","authors":"Ryota Kikuchi, Yusuke Watanabe, Takashi Okuma, Hiroyuki Nakamura, Shinji Abe","doi":"10.1007/s00262-024-03792-5","DOIUrl":"10.1007/s00262-024-03792-5","url":null,"abstract":"<p><p>Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90-10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62-17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer. 多发性原发性肺癌放射学特征明显的结节的免疫基因组特征。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03807-1
Mei-Cheng Chen, Hao-Shuai Yang, Zhi Dong, Lu-Jie Li, Xiang-Min Li, Hong-He Luo, Qiong Li, Ying Zhu

Objectives: To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC).

Methods: The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC.

Results: In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8+ T cells. Single-cell gene analysis demonstrated that CD8+ T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8+ T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR).

Conclusions: Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.

目的为放射学特征明显的多发性原发性肺癌(MPLC)的治疗提供分子和免疫学属性机制方面的见解:方法:从本中心获得 MPLC 的批量 RNA-seq 数据。单原发性肺癌(SPLC)患者的批量 RNA-seq 数据和 CT 图像来自 GSE103584。免疫浸润算法用于研究两组患者免疫微环境的差异。单细胞基因分析用于探讨 MPLC 中免疫细胞的组成和细胞间的通讯关系:结果:在 MPLC 中,发现了 11 个纯磨玻璃不透明结节(pGGN)和 10 个混合 GGN(mGGN),而在 SPLC 中,pGGN 和 mGGN 的数量分别为 18 个和 22 个。在 MPLC 中,与 pGGN 相比,mGGN 的 CD8+ T 细胞浸润显著增加。单细胞基因分析表明,CD8+ T 细胞在 MPLC 免疫细胞间的信号转导中起着核心作用。包括MAFG、RUNX3和TBX21在内的转录因子可能在CD8+ T细胞的调控中起着关键作用。值得注意的是,与SPLC结节中的mGGN和pGGN相比,MPLC结节中肿瘤浸润免疫细胞的数量明显增加,这种差异在mGGN中尤为明显。免疫细胞的比例与合并/肿瘤比率(CTR)呈正相关:我们的研究结果全面描述了早期 MPLC 中 pGGN 和 mGGN 免疫微环境的差异,以及 MPLC 和 SPLC 中 mGGN 和 pGGN 免疫微环境的差异。这些研究结果可为MPLC免疫治疗策略的设计提供证据。
{"title":"Immunogenomic features of radiologically distinctive nodules in multiple primary lung cancer.","authors":"Mei-Cheng Chen, Hao-Shuai Yang, Zhi Dong, Lu-Jie Li, Xiang-Min Li, Hong-He Luo, Qiong Li, Ying Zhu","doi":"10.1007/s00262-024-03807-1","DOIUrl":"10.1007/s00262-024-03807-1","url":null,"abstract":"<p><strong>Objectives: </strong>To provide molecular and immunological attributes mechanistic insights for the management of radiologically distinctive multiple primary lung cancer (MPLC).</p><p><strong>Methods: </strong>The Bulk RNA-seq data of MPLC were obtained from our center. The Bulk RNA-seq data and CT images of patients with single primary lung cancer (SPLC) were obtained from GSE103584. Immune infiltration algorithms were performed to investigate the disparities in the immunological microenvironment between the two groups. Single-cell gene analysis was used to explore immune cells composition and communication relationships between cells in MPLC.</p><p><strong>Results: </strong>In MPLC, 11 pure ground-glass opacity nodules (pGGN) and 10 mixed GGN (mGGN) were identified, while in SPLC, the numbers were 18 pGGN and 22 mGGN, respectively. In MPLC, compared to pGGN, mGGN demonstrated a significantly elevated infiltration of CD8<sup>+</sup> T cells. Single-cell gene analysis demonstrated that CD8<sup>+</sup> T cells play a central role in the signaling among immune cells in MPLC. The transcription factors including MAFG, RUNX3, and TBX21 may play pivotal roles in regulation of CD8<sup>+</sup> T cells. Notably, compared to SPLC nodules for both mGGN and pGGN, MPLC nodules demonstrated a significantly elevated degree of tumor-infiltrating immune cells, with this difference being particularly pronounced in mGGN. There was a positive correlation between the proportion of immune cells and consolidation/tumor ratio (CTR).</p><p><strong>Conclusions: </strong>Our findings provided a comprehensive description about the difference in the immune microenvironment between pGGN and mGGN in early-stage MPLC, as well as between MPLC and SPLC for both mGGN and pGGN. The findings may provide evidence for the design of immunotherapeutic strategies for MPLC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increasing monocytes after lung cancer surgery triggers the outgrowth of distant metastases, causing recurrence. 肺癌手术后单核细胞的增加会诱发远处转移灶的生长,导致复发。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03800-8
Yo Kawaguchi, Keigo Okamoto, Yoko Kataoka, Kohei Shibata, Hiroki Saito, Takuya Shiratori, Keiko Ueda, Yasuhiko Ohshio, Jun Hanaoka

Patients with lung cancer have a high incidence of tumor recurrence even after curative surgical resection. Some reports indicated that immunosuppressive cells induced by surgical stress could contribute to tumor recurrence after surgery; however, the underlying mechanisms are not fully understood. In this study, we found that increased postoperative blood monocytes served as a risk factor for tumor recurrence in 192 patients with non-small cell lung cancer (NSCLC). We established the lung cancer recurrent mouse model after tumor resection and showed that the surgical stress immediately increased the level of serum monocyte chemoattractant protein-1 (MCP-1), which subsequently increased blood monocytes. These blood monocytes were rapidly recruited into distant micrometastases and became tumor growth-promoting tumor associated macrophages (TAMs). Furthermore, even after the blood MCP-1 and monocytes decreased enough 72 h after tumor resection, TAMs in micrometastases remained rich because the MCP-1 secreted by micrometastases themselves continued to recruit monocytes around the tumor. Consequently, tumor resection triggered the outgrowth of distant metastases via the MCP-1-Monocyte-TAM axis. When we administered the MCP-1 inhibitor to the lung cancer recurrent model mice, blood monocytes decreased after tumor resection, and TAMs in micrometastases also dramatically decreased. Finally, peri- and postoperative treatment with the MCP-1 inhibitor suppressed distant metastases after surgery. Targeting the MCP-1-Monocyte-TAM axis may inhibit surgical stress-induced NSCLC recurrence by attenuating postoperative immunosuppressive monocytes in micrometastases.

肺癌患者即使接受了根治性手术切除,肿瘤复发率也很高。一些报道指出,手术应激诱导的免疫抑制细胞可能导致术后肿瘤复发,但其潜在机制尚未完全明了。在这项研究中,我们发现在 192 例非小细胞肺癌(NSCLC)患者中,术后血单核细胞增加是肿瘤复发的一个危险因素。我们建立了肿瘤切除术后肺癌复发小鼠模型,结果表明,手术应激会立即增加血清单核细胞趋化蛋白-1(MCP-1)的水平,从而增加血液中的单核细胞。这些血液单核细胞被迅速招募到远处的微转移灶,成为促进肿瘤生长的肿瘤相关巨噬细胞(TAMs)。此外,即使在肿瘤切除 72 小时后,血液中的 MCP-1 和单核细胞减少到足够多,微转移灶中的 TAMs 仍然很丰富,因为微转移灶本身分泌的 MCP-1 继续招募肿瘤周围的单核细胞。因此,肿瘤切除通过 MCP-1-单核细胞-TAM 轴引发了远处转移灶的生长。当我们给肺癌复发模型小鼠注射 MCP-1 抑制剂时,肿瘤切除后血液中的单核细胞减少,微转移灶中的 TAM 也显著减少。最后,术前和术后使用 MCP-1 抑制剂可抑制术后的远处转移。针对MCP-1-单核细胞-TAM轴,可以通过减少术后微转移灶中的免疫抑制性单核细胞,抑制手术应激诱导的NSCLC复发。
{"title":"Increasing monocytes after lung cancer surgery triggers the outgrowth of distant metastases, causing recurrence.","authors":"Yo Kawaguchi, Keigo Okamoto, Yoko Kataoka, Kohei Shibata, Hiroki Saito, Takuya Shiratori, Keiko Ueda, Yasuhiko Ohshio, Jun Hanaoka","doi":"10.1007/s00262-024-03800-8","DOIUrl":"10.1007/s00262-024-03800-8","url":null,"abstract":"<p><p>Patients with lung cancer have a high incidence of tumor recurrence even after curative surgical resection. Some reports indicated that immunosuppressive cells induced by surgical stress could contribute to tumor recurrence after surgery; however, the underlying mechanisms are not fully understood. In this study, we found that increased postoperative blood monocytes served as a risk factor for tumor recurrence in 192 patients with non-small cell lung cancer (NSCLC). We established the lung cancer recurrent mouse model after tumor resection and showed that the surgical stress immediately increased the level of serum monocyte chemoattractant protein-1 (MCP-1), which subsequently increased blood monocytes. These blood monocytes were rapidly recruited into distant micrometastases and became tumor growth-promoting tumor associated macrophages (TAMs). Furthermore, even after the blood MCP-1 and monocytes decreased enough 72 h after tumor resection, TAMs in micrometastases remained rich because the MCP-1 secreted by micrometastases themselves continued to recruit monocytes around the tumor. Consequently, tumor resection triggered the outgrowth of distant metastases via the MCP-1-Monocyte-TAM axis. When we administered the MCP-1 inhibitor to the lung cancer recurrent model mice, blood monocytes decreased after tumor resection, and TAMs in micrometastases also dramatically decreased. Finally, peri- and postoperative treatment with the MCP-1 inhibitor suppressed distant metastases after surgery. Targeting the MCP-1-Monocyte-TAM axis may inhibit surgical stress-induced NSCLC recurrence by attenuating postoperative immunosuppressive monocytes in micrometastases.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Impact of fludarabine and treosulfan on ovarian tumor cells and mesothelin chimeric antigen receptor T cells. 更正:氟达拉滨和曲硫凡对卵巢肿瘤细胞和间皮素嵌合抗原受体 T 细胞的影响。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03813-3
Ibrahim El-Seraf, Isabella Micallef Nilsson, Alina Moter, Zhe Duan, Jonas Mattsson, Isabelle Magalhaes
{"title":"Correction to: Impact of fludarabine and treosulfan on ovarian tumor cells and mesothelin chimeric antigen receptor T cells.","authors":"Ibrahim El-Seraf, Isabella Micallef Nilsson, Alina Moter, Zhe Duan, Jonas Mattsson, Isabelle Magalhaes","doi":"10.1007/s00262-024-03813-3","DOIUrl":"10.1007/s00262-024-03813-3","url":null,"abstract":"","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
SAFFRON-104: a phase Ib/II study of sitravatinib alone or with tislelizumab in advanced hepatocellular carcinoma and gastric cancer/gastroesophageal junction cancer. SAFFRON-104:一项针对晚期肝细胞癌和胃癌/胃食管交界处癌的西曲替尼单药或联合替赛珠单抗的Ib/II期研究。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03806-2
Jin Li, Yuxian Bai, Zhendong Chen, Jieer Ying, Yabing Guo, Weijia Fang, Feng Zhang, Jianping Xiong, Tao Zhang, Zhiqiang Meng, Jingdong Zhang, Zhenggang Ren, Chunyi Hao, Yajin Chen, Xiaoyan Lin, Hongming Pan, Fuxiang Zhou, Xin Li, Fan Yu, Juan Zhang, Zhang Zhang, Shukui Qin

Background: Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC).

Methods: Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1-naïve or -treated HCC and anti-PD-(L)1-naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II).

Results: At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7-36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7-49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4-30.2) with anti-PD-(L)1-naïve HCC, 9.5% (95% CI 1.2-30.4) with anti-PD-(L)1-treated HCC, and 16.1% (95% CI 5.5-33.7) in patients with anti-PD-(L)1-naïve GC/GEJC.

Conclusions: Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.

背景介绍西曲拉替尼是一种谱系选择性酪氨酸激酶抑制剂,靶向TAM(TYRO3、AXL、MER)、VEGFR-2、KIT和MET。SAFFRON-104(NCT03941873)是一项多队列Ib/II期研究,研究对象是晚期肝细胞癌(HCC)或胃癌/胃食管交界处癌(GC/GEJC)患者,研究方法是西曲替尼联合/不联合抗程序性细胞死亡蛋白1(PD-1)抗体tislelizumab:符合条件的患者均为组织学/细胞学确诊的晚期HCC或GC/GEJC。I期确定了西曲拉替尼联合/不联合替赛珠单抗的II期推荐剂量(RP2D)。II期评估了西曲拉替尼单药治疗预处理HCC患者,以及西曲拉替尼联合替赛珠单抗治疗抗PD-(L)1-naï或治疗HCC和抗PD-(L)1-naïGC/GEJC患者。主要终点是安全性/耐受性(I期)和客观应答率(ORR)(II期):截至数据截止日(2023 年 3 月 31 日),共有 111 例患者入组,其中 102 例疗效有效(中位随访时间为 9.1 个月 [范围:0.7-36.9])。西曲拉替尼的RP2D被确定为120毫克,每天口服一次。在接受西曲拉替尼单药治疗和西曲拉替尼联合替赛珠单抗治疗的患者中,分别有14名(51.9%)和42名(50.0%)患者发生了≥3级的治疗相关不良事件。接受西曲替尼单药治疗的HCC预处理患者的ORR为25%(95%置信区间[CI]:8.7-49.1)。在接受西曲替尼联合替赛利珠单抗治疗的患者中,抗PD-(L)1-无效的HCC患者的ORR为11.5%(95% CI 2.4-30.2),抗PD-(L)1-治疗的HCC患者的ORR为9.5%(95% CI 1.2-30.4),抗PD-(L)1-无效的GC/GEJC患者的ORR为16.1%(95% CI 5.5-33.7):在晚期HCC和GC/GEJC患者中,西曲拉替尼联合/不联合替赛珠单抗的耐受性普遍良好,并显示出初步的抗肿瘤活性。
{"title":"SAFFRON-104: a phase Ib/II study of sitravatinib alone or with tislelizumab in advanced hepatocellular carcinoma and gastric cancer/gastroesophageal junction cancer.","authors":"Jin Li, Yuxian Bai, Zhendong Chen, Jieer Ying, Yabing Guo, Weijia Fang, Feng Zhang, Jianping Xiong, Tao Zhang, Zhiqiang Meng, Jingdong Zhang, Zhenggang Ren, Chunyi Hao, Yajin Chen, Xiaoyan Lin, Hongming Pan, Fuxiang Zhou, Xin Li, Fan Yu, Juan Zhang, Zhang Zhang, Shukui Qin","doi":"10.1007/s00262-024-03806-2","DOIUrl":"10.1007/s00262-024-03806-2","url":null,"abstract":"<p><strong>Background: </strong>Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (TYRO3, AXL, MER), VEGFR-2, KIT, and MET. SAFFRON-104 (NCT03941873) was a multicohort phase Ib/II study investigating sitravatinib with/without tislelizumab, an anti-programmed cell death protein 1 (PD-1) antibody, in patients with advanced hepatocellular carcinoma (HCC) or gastric cancer/gastroesophageal junction cancer (GC/GEJC).</p><p><strong>Methods: </strong>Eligible patients had histologically/cytologically confirmed advanced HCC or GC/GEJC. Phase I determined the recommended phase II dose (RP2D) of sitravatinib with/without tislelizumab. Phase II evaluated sitravatinib monotherapy in patients with pretreated HCC, and sitravatinib plus tislelizumab in anti-PD-(L)1-naïve or -treated HCC and anti-PD-(L)1-naïve GC/GEJC. Primary endpoints were safety/tolerability (phase I) and objective response rate (ORR) (phase II).</p><p><strong>Results: </strong>At data cutoff (March 31, 2023), 111 patients were enrolled; 102 were efficacy-evaluable (median study follow-up 9.1 months [range: 0.7-36.9]). The RP2D of sitravatinib was determined as 120 mg orally once daily. In patients receiving sitravatinib monotherapy and sitravatinib in combination with tislelizumab, grade ≥ 3 treatment-related adverse events occurred in 14 (51.9%) and 42 (50.0%) patients, respectively. The ORR was 25% (95% confidence interval [CI]: 8.7-49.1) in patients with pretreated HCC receiving sitravatinib monotherapy. In patients receiving sitravatinib with tislelizumab, the ORR was 11.5% (95% CI 2.4-30.2) with anti-PD-(L)1-naïve HCC, 9.5% (95% CI 1.2-30.4) with anti-PD-(L)1-treated HCC, and 16.1% (95% CI 5.5-33.7) in patients with anti-PD-(L)1-naïve GC/GEJC.</p><p><strong>Conclusions: </strong>Sitravatinib with/without tislelizumab was generally well tolerated and showed preliminary antitumor activity in patients with advanced HCC and GC/GEJC.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy. 接受 PD-1/L1 抑制剂单药治疗的 NSCLC 患者治疗前和治疗中可溶性免疫介质及肿瘤微环境的特征。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03781-8
Daiki Murata, Koichi Azuma, Kenta Murotani, Akihiko Kawahara, Yuuya Nishii, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino

Background: Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge.

Methods: Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed.

Results: Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17.

Conclusion: We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.

背景:尽管ICI单药治疗具有良好的疗效,但大多数非小细胞肺癌(NSCLC)患者并无反应。因此,确定哪些患者能从 ICI 治疗中获得最佳疗效仍是一项挑战:在接受 ICI 单药治疗的 183 例晚期或复发性 NSCLC 患者中,我们分析了 110 例可获得治疗前和治疗后血浆样本的患者。在开始接受 ICI 治疗时和 6 周后,我们测定了 73 种可溶性免疫介质。为了找出有用的生物标志物,我们分析了可溶性免疫介质在治疗前和治疗中的水平变化与患者生存期的关系。我们还分析了治疗前或治疗中生物标志物与irAE发展、PD-L1表达、CD8+ TIL密度以及中性粒细胞与淋巴细胞比值(NLR)的关系:单变量分析显示,治疗前生物标志物包括6种免疫介质,而治疗中生物标志物包括8种免疫介质。多变量分析显示,治疗前生物标志物包括4种免疫介质(CCL19、CCL21、CXCL5、CXCL10),而治疗中生物标志物包括5种免疫介质(CCL7、CCL19、CCL23、CCL25、IL-32)。IrAE 的发生与治疗期间 CCL23 的变化有关。PD-L1 的表达与治疗前 TNFSF13B 的水平和治疗中 CCL25 的变化有关。CD8+ TIL密度与治疗前的CXCL10水平相关,而NLR与治疗前的CCL13和CCL17水平相关:我们发现了几种可溶性免疫介质,它们是接受 ICI 单药治疗的 NSCLC 患者治疗前和治疗中生存的生物标志物。其中一些生物标志物与其他可能的预测因子相关,包括irAE的发展、PD-L1的表达、CD8+ TIL密度和NLR。需要进一步开展大规模研究,为接受 ICI 单药治疗的 NSCLC 患者建立生物标志物。
{"title":"Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy.","authors":"Daiki Murata, Koichi Azuma, Kenta Murotani, Akihiko Kawahara, Yuuya Nishii, Takaaki Tokito, Tetsuro Sasada, Tomoaki Hoshino","doi":"10.1007/s00262-024-03781-8","DOIUrl":"10.1007/s00262-024-03781-8","url":null,"abstract":"<p><strong>Background: </strong>Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge.</p><p><strong>Methods: </strong>Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed.</p><p><strong>Results: </strong>Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17.</p><p><strong>Conclusion: </strong>We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma. 在切除的人类食管腺癌中,PD-1 和 CD39 阳性 CD8+ 组织常驻 T 淋巴细胞的高比例与更好的临床预后相关。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-05 DOI: 10.1007/s00262-024-03799-y
Samuel L Hill, Gessa Sugiyarto, Jack Harrington, Edward James, Timothy J Underwood, Tim Elliott

Objective: To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.

Design: Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed.

Results: A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity.

Conclusion: Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.

目的了解食管腺癌(OAC)CD8+肿瘤浸润淋巴细胞(TIL)区系的淋巴细胞衰竭标志物和组织驻留情况,并确定不同治疗反应背后的可能原因:设计:通过流式细胞术评估了44例接受根治性切除术的食管腺癌患者的肿瘤样本中抗原经验丰富的TIL以及活化和衰竭标记物的存在情况。对 PD-1 和 CD39 阳性的 OAC TILs 群体进行分拣,并使用改良的 SmartSeq2 方案进行批量 RNA 测序。完成了流式细胞术功能评估:结果:抗原经验丰富的 CD8+ OAC TILs 比例越高,术后生存率越高;同时,这些 TILs 的 PD-1 和 CD39 双阳性 (DP) 也与预后有显著相关性。这些双阳性 TIL 中的少数群体对衰竭标记物 TIM3 和 LAG3 呈阳性。对 PD-1 和 CD39 DP TIL 的转录组学评估显示,组织常驻记忆 T 淋巴细胞(TRM)表型的富集与其他癌症生存率的提高有关,流式细胞术显示的典型 TRM 标记 CD103 阳性则进一步证实了这一点。这一群体在其转录组图谱和流式细胞术评估中都显示出了维持功能的能力,并保留了增殖能力:结论:切除的 OAC 会受到 PD-1 和 CD39 DP TIL 的不同程度浸润,淋巴细胞中这种 DP TIL 的丰富程度与生存率的提高有关。与 DN 相比,这种 DP 群体的 TIM3 和 LAG3 阳性率更高,但仍不高,而且符合有功能能力的 TRM 表型。
{"title":"High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.","authors":"Samuel L Hill, Gessa Sugiyarto, Jack Harrington, Edward James, Timothy J Underwood, Tim Elliott","doi":"10.1007/s00262-024-03799-y","DOIUrl":"10.1007/s00262-024-03799-y","url":null,"abstract":"<p><strong>Objective: </strong>To understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.</p><p><strong>Design: </strong>Tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed.</p><p><strong>Results: </strong>A higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity.</p><p><strong>Conclusion: </strong>Resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11377377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Cancer Immunology, Immunotherapy
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1