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HLA-G neo-expression modifies genetic programs governing tumor cell lines. HLA-G 的新表达改变了肿瘤细胞系的基因程序。
IF 5.4 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-03 DOI: 10.1007/s00262-024-03768-5
Diana Tronik-Le Roux, Marina Daouya, Isabelle Poras, François Desgrandchamps, Edgardo D Carosella

The development of immunotherapies has proved to be clinically encouraging to re-establish the immune function modified by the expression of immune inhibitory molecules in tumors. However, there are still patients with poor survival rates following treatment. The elucidation of molecular mechanisms triggered by the neo-expression of particular IC in tumors would constitute a major step toward better understanding tumor evolution and would help to design future clinical protocols. To this end, we investigate the modifications triggered by the neo-expression of the immune checkpoints HLA-G in ccRCC tumor cells. We demonstrate, for the first time, that HLA-G modifies key genes implicated mainly in tumor development, angiogenesis, calcium flow and mitochondria dynamics. The involvement of HLA-G on the expression of genes belonging to these pathways such as ADAM-12, NCAM1 and NRP1 was confirmed by the CRISPR/Cas9-mediated edition of HLA-G. The data reveal multifaceted roles of HLA-G in tumor cells which are far beyond the well-known function of HLA-G in the immune anti-tumor response. This warrants further investigation of HLA-G and these new partners in tumors of different origin so as to propose future new treatments to improve health patient's outcome.

免疫疗法的发展在临床上证明是令人鼓舞的,它可以重建因肿瘤中免疫抑制分子的表达而改变的免疫功能。然而,仍有一些患者在接受治疗后生存率很低。阐明特定 IC 在肿瘤中的新表达所引发的分子机制将是更好地理解肿瘤演变的重要一步,并有助于设计未来的临床方案。为此,我们研究了免疫检查点 HLA-G 在 ccRCC 肿瘤细胞中的新表达所引发的改变。我们首次证明,HLA-G 会改变主要与肿瘤发生、血管生成、钙流和线粒体动力学有关的关键基因。通过 CRISPR/Cas9 介导的 HLA-G 基因编辑,证实了 HLA-G 参与了 ADAM-12、NCAM1 和 NRP1 等这些通路基因的表达。这些数据揭示了 HLA-G 在肿瘤细胞中的多方面作用,远远超出了人们所熟知的 HLA-G 在免疫抗肿瘤反应中的功能。这就需要进一步研究 HLA-G 和这些新伙伴在不同来源肿瘤中的作用,以便提出未来的新疗法,改善患者的健康状况。
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引用次数: 0
Immunotherapy may be more appropriate for ERBB2 low-expressing extramammary paget's disease patients: a prognosis analysis and exploration of targeted therapy and immunotherapy of extramammary paget's disease patients. 免疫疗法可能更适合ERBB2低表达的乳腺外乳头状瘤病患者:乳腺外乳头状瘤病患者的预后分析及靶向治疗和免疫疗法探索。
IF 5.4 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-03 DOI: 10.1007/s00262-024-03846-8
Jiawen Yang, Yurong Chen, Xiuyuan Zhang, Ziyan Tong, Shanshan Weng, Ning Zhu, Ying Yuan

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy characterized by its uncertain etiology and metastatic potential. Surgery remains the first-line clinical treatment for EMPD, but the efficacy of radiotherapy and chemotherapy remains to be fully evaluated, and new therapies for EMPD are urgently needed. In this study, we initially screened 815 EMPD patients in the Surveillance, Epidemiology, and End Results (SEER) database and analyzed their clinical features and prognostic factors. Using the dataset from the Genome Sequence Archive (GSA) database, we subsequently conducted weighted gene coexpression network analysis (WGCNA), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analyses, grouping the samples based on EMPD disease status and the levels of ERBB2 expression. The prognostic analysis based on the SEER database identified increased age at diagnosis, distant metastasis, and receipt of radiotherapy as independent risk factors for EMPD. Moreover, our results indicated that patients who received chemotherapy had worse prognoses than those who did not, highlighting the urgent need for novel treatment approaches for EMPD. Functional analysis of the GSA-derived dataset revealed that EMPD tissues were significantly enriched in immune-related pathways compared with normal skin tissues. Compared with those with high ERBB2 expression, tissues with low ERBB2 expression displayed greater immunogenicity and enrichment of immune pathways, particularly those related to B cells. These findings suggest that patients with low ERBB2 expression are likely to benefit from immunotherapy, especially B-cell-related immunotherapy.

乳腺外Paget病(EMPD)是一种罕见的皮肤恶性肿瘤,其特点是病因不明确且具有转移潜力。手术仍是 EMPD 的一线临床治疗方法,但放疗和化疗的疗效仍有待全面评估,EMPD 急需新疗法。在这项研究中,我们首先从监测、流行病学和最终结果(SEER)数据库中筛选了815名EMPD患者,并分析了他们的临床特征和预后因素。利用基因组序列档案(GSA)数据库中的数据集,我们随后进行了加权基因共表达网络分析(WGCNA)、基因组富集分析(GSEA)、基因组变异分析(GSVA)和免疫浸润分析,并根据EMPD疾病状态和ERBB2表达水平对样本进行了分组。基于SEER数据库的预后分析发现,诊断时年龄增大、远处转移和接受过放疗是EMPD的独立危险因素。此外,我们的研究结果表明,接受化疗的患者比未接受化疗的患者预后更差,这凸显了对新型 EMPD 治疗方法的迫切需求。GSA衍生数据集的功能分析显示,与正常皮肤组织相比,EMPD组织的免疫相关通路明显丰富。与ERBB2高表达的组织相比,ERBB2低表达的组织显示出更强的免疫原性和更丰富的免疫通路,尤其是与B细胞相关的通路。这些研究结果表明,ERBB2表达量低的患者有可能从免疫疗法中获益,尤其是与B细胞相关的免疫疗法。
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引用次数: 0
PD-L1+ neutrophils induced NETs in malignant ascites is a potential biomarker in HCC. 恶性腹水中PD-L1+中性粒细胞诱导的NET是HCC的潜在生物标志物。
IF 5.4 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-03 DOI: 10.1007/s00262-024-03833-z
Xiaoyu Sun, Yaoqi Gui, Tai Yang, Lingbing Chen, Yi Zhang, Ling Yan, Weixian Chen, Bo Wang

Background: Since differentiating malignant ascites from benign ascites has always been a clinical difficult, recognition of novel biomarkers in malignant ascites of hepatocellular carcinoma (HCC) patients could be helpful for establishing a diagnosis for HCC patients with ascitic fluids.

Methods: Thirty-five HCC patients with malignant ascites and chronic liver diseases patients with benign ascites were enrolled. Serum and ascites specimens were collected to determine TAN subpopulations and NETs concentration. Then, the correlation between ascitic NETs levels and clinical features were analyzed, and ROC curves were generated to evaluate the diagnostic value of NETs. For in vitro study, fresh neutrophils were employed to explore the underlying mechanism of TAN polarization and NETs formation using RNAseq analysis.

Results: Significantly increased pro-tumor PD-L1+ TANs and higher lactate levels were measured in HCC ascites. RNAseq data showed that lactate regulated genes expression involving PD-L1 expression and NETs formation, suggesting that ascitic lactate might be responsible for tumor progression in TME. Then, NETs-related markers including calprotectin, dsDNA, CitH3, MPO and MPO-DNA were found dramatically elevated in malignant ascites. Next, correlation analysis revealed that ascitic NETs levels positively correlated with LDH, a classic ascitic biochemical indicator. Furthermore, we identified the diagnostic values of NETs in discriminating malignant ascites from benign ascites.

Conclusions: Our findings highlighted that elevated ascitic NETs served as a biomarker in HCC patients with malignant ascites, which provided useful insights for both clinical and basic research for malignant ascites diagnosis and management.

背景:由于恶性腹水与良性腹水的鉴别一直是临床难题,因此识别肝细胞癌(HCC)患者恶性腹水中的新型生物标志物有助于对有腹水的 HCC 患者进行确诊:方法:研究人员招募了 35 名患有恶性腹水的 HCC 患者和患有良性腹水的慢性肝病患者。收集血清和腹水标本,测定 TAN 亚群和 NETs 浓度。然后,分析腹水 NETs 水平与临床特征之间的相关性,并生成 ROC 曲线以评估 NETs 的诊断价值。体外研究采用新鲜中性粒细胞,利用RNAseq分析探讨TAN极化和NETs形成的内在机制:结果:在 HCC 腹水中测得了显著增加的亲肿瘤 PD-L1+ TAN 和较高的乳酸盐水平。RNAseq数据显示,乳酸调节涉及PD-L1表达和NETs形成的基因表达,这表明腹水乳酸可能是TME中肿瘤进展的原因。恶性腹水中的钙蛋白、dsDNA、CitH3、MPO和MPO-DNA等NETs相关标记物显著升高。接着,相关分析表明,腹水 NETs 水平与腹水生化指标 LDH 呈正相关。此外,我们还发现了 NETs 在区分恶性腹水和良性腹水方面的诊断价值:我们的研究结果表明,腹腔 NETs 升高可作为 HCC 恶性腹水患者的生物标志物,这为恶性腹水诊断和管理的临床和基础研究提供了有益的启示。
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引用次数: 0
Correction to: Inhibition of glycolysis enhances the efficacy of immunotherapy via PDK‑mediated upregulation of PD‑L1. 更正为抑制糖酵解可通过 PDK 介导的 PD-L1 上调增强免疫疗法的疗效。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-17 DOI: 10.1007/s00262-024-03811-5
Ruizhi Zhang, Gan Mao, Yu Tang, Chong Li, Yisong Gao, Wenxiang Nie, Tianyu Song, Suao Liu, Peng Zhang, Kaixiong Tao, Wei Li
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引用次数: 0
Bronchoalveolar lavage fluid analysis in patients with checkpoint inhibitor pneumonitis 检查点抑制剂肺炎患者支气管肺泡灌洗液分析
IF 5.8 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-13 DOI: 10.1007/s00262-024-03834-y
Ruxuan Chen, Yujie Shi, Nan Fang, Chi Shao, Hui Huang, Ruili Pan, Yan Xu, Mengqi Wang, Xiangning Liu, Kai Xu, Rui Zhu, Mengzhao Wang

Background

Checkpoint inhibitor pneumonitis (CIP) is a relatively uncommon but potentially life-threatening immune-related adverse event (irAE). Lung biopsies have not been commonly performed for CIP patients. Bronchoalveolar lavage fluid (BALF) analysis is a useful diagnostic approach for interstitial lung disease. However, BALF features were inconsistent across different studies.

Methods

We retrospectively reviewed the medical records of 154 patients with pathologically confirmed malignancies and suffering from CIPs between July 2018 and December 2022. Patients who had bronchoalveolar lavage (BAL) data available were enrolled in our study. Patient clinical, laboratory, radiological and follow-up data were reviewed and analyzed.

Results

The BALF differential cell count and lymphocyte subset analysis were performed for 42 CIP patients. There were 32 males (76.2%). The mean age at diagnosis of CIP was 62.0 ± 10.4 (range: 31–78) years. The median time to onset of CIP was 98.5 days after the start of immunotherapy. There were 18 patients (42.9%) with low-grade CIPs and 24 patients (57.1%) with high-grade CIPs. The mean lymphocyte percentage was 36.7 ± 22.5%. There were 34 (81%) CIP patients with a lymphocytic cellular pattern. The median ratio of CD3+CD4+/CD3+CD8+ lymphocytes was 0.5 (0.3, 1.0). The ratio was less than 1.0 for 31 CIP patients (73.8%). However, there was no significant difference in the BALF features between patients with low-grade CIPs and those with high-grade CIPs.

Conclusions

The CD3+CD8+ lymphocytosis pattern was the main inflammatory profile in the BALF of CIP patients in this cohort. Targeting CD3+CD8+ lymphocytes might be a treatment option for CIPs.

背景检查点抑制剂肺炎(CIP)是一种相对少见但可能危及生命的免疫相关不良事件(irAE)。对 CIP 患者进行肺活检并不常见。支气管肺泡灌洗液(BALF)分析是诊断间质性肺病的有效方法。然而,不同研究中的 BALF 特征并不一致。方法我们回顾性地查看了 2018 年 7 月至 2022 年 12 月间 154 例经病理证实为恶性肿瘤的 CIP 患者的病历。有支气管肺泡灌洗(BAL)数据的患者被纳入我们的研究。对患者的临床、实验室、放射学和随访数据进行了回顾和分析。结果对42名CIP患者进行了BALF差异细胞计数和淋巴细胞亚群分析。其中男性 32 人(76.2%)。确诊 CIP 的平均年龄为 62.0 ± 10.4(31-78)岁。CIP 发病的中位时间为免疫疗法开始后的 98.5 天。低级别 CIP 患者有 18 人(42.9%),高级别 CIP 患者有 24 人(57.1%)。平均淋巴细胞百分比为 36.7 ± 22.5%。34例(81%)CIP患者的细胞形态为淋巴细胞。CD3+CD4+/CD3+CD8+ 淋巴细胞的中位比率为 0.5 (0.3, 1.0)。31 名 CIP 患者(73.8%)的比率小于 1.0。结论 CD3+CD8+ 淋巴细胞增多模式是该队列中 CIP 患者 BALF 的主要炎症特征。靶向 CD3+CD8+ 淋巴细胞可能是治疗 CIP 的一种选择。
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引用次数: 0
Single-cell RNA sequencing to map tumor heterogeneity in gastric carcinogenesis paving roads to individualized therapy 用单细胞 RNA 测序绘制胃癌发生过程中的肿瘤异质性图谱,为个体化治疗铺平道路
IF 5.8 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-13 DOI: 10.1007/s00262-024-03820-4
Jiao Xu, Bixin Yu, Fan Wang, Jin Yang

Gastric cancer (GC) is a highly heterogeneous disease with a complex tumor microenvironment (TME) that encompasses multiple cell types including cancer cells, immune cells, stromal cells, and so on. Cancer-associated cells could remodel the TME and influence the progression of GC and therapeutic response. Single-cell RNA sequencing (scRNA-seq), as an emerging technology, has provided unprecedented insights into the complicated biological composition and characteristics of TME at the molecular, cellular, and immunological resolutions, offering a new idea for GC studies. In this review, we discuss the novel findings from scRNA-seq datasets revealing the origin and evolution of GC, and scRNA-seq is a powerful tool for investigating transcriptional dynamics and intratumor heterogeneity (ITH) in GC. Meanwhile, we demonstrate that the vital immune cells within TME, including T cells, B cells, macrophages, and stromal cells, play an important role in the disease progression. Additionally, we also overview that how scRNA-seq facilitates our understanding about the effects on individualized therapy of GC patients. Spatial transcriptomes (ST) have been designed to determine spatial distribution and capture local intercellular communication networks, enabling a further understanding of the relationship between the spatial background of a particular cell and its functions. In summary, scRNA-seq and other single-cell technologies provide a valuable perspective for molecular and pathological disease characteristics and hold promise for advancing basic research and clinical practice in GC.

胃癌(GC)是一种高度异质性疾病,其肿瘤微环境(TME)十分复杂,包括癌细胞、免疫细胞、基质细胞等多种细胞类型。癌症相关细胞可重塑肿瘤微环境,并影响癌症的进展和治疗反应。单细胞 RNA 测序(scRNA-seq)作为一种新兴技术,从分子、细胞和免疫学的角度为 TME 复杂的生物组成和特征提供了前所未有的见解,为 GC 研究提供了一种新思路。在这篇综述中,我们讨论了 scRNA-seq 数据集揭示 GC 起源和进化的新发现,scRNA-seq 是研究 GC 转录动态和肿瘤内异质性(ITH)的有力工具。同时,我们证明了TME内的重要免疫细胞,包括T细胞、B细胞、巨噬细胞和基质细胞,在疾病进展中发挥着重要作用。此外,我们还概述了 scRNA-seq 如何促进我们对 GC 患者个体化治疗效果的理解。空间转录组(ST)旨在确定空间分布并捕捉局部细胞间通讯网络,从而进一步了解特定细胞的空间背景与其功能之间的关系。总之,scRNA-seq 和其他单细胞技术为了解疾病的分子和病理特征提供了宝贵的视角,有望推动 GC 的基础研究和临床实践。
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引用次数: 0
Genomic and molecular alterations associated with primary resistance to immune checkpoint inhibitors 与免疫检查点抑制剂原发性耐药性相关的基因组和分子改变
IF 5.8 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-13 DOI: 10.1007/s00262-024-03825-z
Jyoti Malhotra, Subhajyoti De, Kim Nguyen, Percy Lee, Victoria Villaflor

The clinical response to immune checkpoint inhibitors may vary by tumor type and many tumors present with either primary or acquired resistance to immunotherapy. Improved understanding of the molecular and immunologic mechanisms underlying immunotherapy resistance is essential for developing biomarkers and for guiding the optimum approach to selecting treatment regimens and sequencing. This is increasingly important for tumors with primary resistance as effective biomarkers in this setting can guide clinicians about appropriate treatment regimen selection in the first-line setting. Multiple potential biological mechanisms of primary resistance have been proposed but most are yet to be validated in prospective clinical cohorts. Individual biomarkers have poor specificity and sensitivity, and the development of validated and integrated predictive models may guide which patient will benefit from monotherapy versus combination therapy. In this review, we discuss the emerging data identifying the molecular mechanisms of primary resistance to immunotherapy and explore potential therapeutic strategies to target these.

不同类型的肿瘤对免疫检查点抑制剂的临床反应可能不同,许多肿瘤对免疫疗法存在原发性或获得性耐药性。进一步了解免疫疗法耐药性的分子和免疫学机制对于开发生物标记物、指导选择治疗方案和排序的最佳方法至关重要。这对于原发性耐药的肿瘤越来越重要,因为在这种情况下,有效的生物标志物可以指导临床医生在一线治疗中选择适当的治疗方案。目前已提出了多种原发性耐药的潜在生物机制,但大多数都有待在前瞻性临床队列中验证。单个生物标志物的特异性和敏感性较差,开发经过验证的综合预测模型可指导哪些患者将从单药治疗或联合治疗中获益。在本综述中,我们将讨论确定免疫疗法原发性耐药分子机制的新数据,并探讨针对这些机制的潜在治疗策略。
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引用次数: 0
Recent clinical researches and technological development in TIL therapy TIL 疗法的最新临床研究和技术发展
IF 5.8 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-12 DOI: 10.1007/s00262-024-03793-4
Satoko Matsueda, Lei Chen, Hongmei Li, Hui Yao, Fuli Yu

Tumor-infiltrating lymphocyte (TIL) therapy represents a groundbreaking advancement in the solid cancer treatment, offering new hope to patients and their families with high response rates and long overall survival. TIL therapy involves extracting immune cells from a patient's tumor tissue, expanding them ex vivo, and infusing them back into the patient to target and eliminate cancer cells. This revolutionary approach harnesses the power of the immune system to combat cancers, ushering in a new era of T cell-based therapies along with CAR-T and TCR-therapies. In this comprehensive review, we aim to elucidate the remarkable potential of TIL therapy by delving into recent advancements in basic and clinical researches. We highlight on the evolving landscape of TIL therapy as a prominent immunotherapeutic strategy, its multifaceted applications, and the promising outcomes. Additionally, we explore the future horizons of TIL therapy, next-generation TILs, and combination therapy, to overcome the limitations and improve clinical efficacy of TIL therapy.

肿瘤浸润淋巴细胞(TIL)疗法是实体瘤治疗领域的突破性进展,它为患者及其家属带来了新的希望,因为这种疗法的反应率高、总生存期长。TIL 疗法包括从患者的肿瘤组织中提取免疫细胞,将其体外扩增,然后将其回输到患者体内,以靶向消除癌细胞。这种革命性的方法利用免疫系统的力量来对抗癌症,与 CAR-T 和 TCR 疗法一起开创了基于 T 细胞疗法的新时代。在这篇综述中,我们将深入探讨基础和临床研究的最新进展,旨在阐明 TIL 疗法的巨大潜力。我们重点介绍了 TIL 疗法作为一种重要的免疫治疗策略不断发展的情况、其多方面的应用以及充满希望的成果。此外,我们还探讨了 TIL 疗法、下一代 TILs 和联合疗法的未来前景,以克服 TIL 疗法的局限性并提高其临床疗效。
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引用次数: 0
A monoclonal antibody recognizing CD98 on human embryonic stem cells shows anti-tumor activity in hepatocellular carcinoma xenografts 识别人类胚胎干细胞 CD98 的单克隆抗体在肝细胞癌异种移植中显示出抗肿瘤活性
IF 5.8 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-11 DOI: 10.1007/s00262-024-03827-x
Keunpyo Lim, San Ha Han, Sein Han, Ji Yoon Lee, Hong Seo Choi, Dongho Choi, Chun Jeih Ryu

CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied. In this study, we generated a panel of monoclonal antibodies (MAbs) against surface proteins on human embryonic stem cells (hESCs). NPB15, one of the MAbs, bound to hESCs and various cancer cells, including HCC cells and non-small cell lung carcinoma (NSCLC) cells, but not to peripheral blood mononuclear cells (PBMCs) and primary hepatocytes. Immunoprecipitation and mass spectrometry identified the target antigen of NPB15 as CD98. CD98 depletion decreased cell proliferation, clonogenic survival, and migration and induced apoptosis in HCC cells. In addition, CD98 depletion decreased the expression of cancer stem cell (CSC) markers in HCC cells. In tumorsphere cultures, the expression of CD98 interacting with NPB15 was significantly increased, as were known CSC markers. After cell sorting by NPB15, cells with high expression of CD98 (CD98-high) showed higher clonogenic survival than cells with low expression of CD98 (CD98-low) in HCC cells, suggesting CD98 as a potential CSC marker on HCC cells. The chimeric version of NPB15 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells in vitro. NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients.

CD98 又称 SLC3A2,是一种由氨基酸转运体组成的多功能细胞表面分子。CD98 在多种组织中普遍表达,但在癌症组织中的表达水平高于正常组织。在大多数肝细胞癌(HCC)患者中,CD98 也会上调;然而,CD98 在 HCC 细胞中的功能却鲜有研究。在这项研究中,我们生成了一组针对人类胚胎干细胞(hESCs)表面蛋白的单克隆抗体(MAbs)。其中一种单克隆抗体NPB15能与hESCs和各种癌细胞(包括HCC细胞和非小细胞肺癌(NSCLC)细胞)结合,但不能与外周血单核细胞(PBMCs)和原代肝细胞结合。免疫沉淀和质谱分析确定了 NPB15 的靶抗原为 CD98。删除 CD98 可减少 HCC 细胞的增殖、克隆存活和迁移,并诱导细胞凋亡。此外,去掉 CD98 还能降低 HCC 细胞中癌症干细胞(CSC)标志物的表达。在肿瘤球培养物中,与 NPB15 相互作用的 CD98 表达明显增加,已知的 CSC 标志物也是如此。用 NPB15 进行细胞分选后,在 HCC 细胞中,CD98 高表达的细胞(CD98-高)比 CD98 低表达的细胞(CD98-低)有更高的克隆存活率,这表明 CD98 是 HCC 细胞潜在的 CSC 标记。嵌合型 NPB15 能够在体外诱导 HCC 细胞产生抗体依赖性细胞毒性(ADCC)。NPB15 注射液在 HCC 异种移植小鼠模型中显示出抗肿瘤活性。这些结果表明,NPB15 有可能被开发成治疗 HCC 患者的抗体。
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引用次数: 0
Adding-on nivolumab to chemotherapy-stabilized patients is associated with improved survival in advanced pancreatic ductal adenocarcinoma. 在化疗稳定的晚期胰腺导管腺癌患者中增加尼妥珠单抗可提高生存率。
IF 4.6 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-09-09 DOI: 10.1007/s00262-024-03821-3
Shih-Hung Yang, Sung-Hsin Kuo, Jen-Chieh Lee, Bang-Bin Chen, Yan-Shen Shan, Yu-Wen Tien, Sz-Chi Chiu, Ann-Lii Cheng, Kun-Huei Yeh

Background: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy.

Patients and methods: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM).

Results: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5-19.0), 2.4 (95% CI 1.2-3.6), and 1.1 (95% CI 1.0-1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5-25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8-16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone.

Conclusion: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy.

背景:由于疗效甚微,免疫检查点抑制剂(ICIs)很少用于治疗晚期胰腺导管腺癌(PDAC):本研究纳入了92例连续确诊为晚期或复发性PDAC的患者,这些患者接受了基于nivolumab的治疗。采用单变量和多变量分析确定预后因素。使用倾向评分匹配法(PSM)选择了301名接受姑息化疗但未使用ICIs的PDAC患者作为对照组进行比较:nivolumab治疗后的中位总生存期(OS)分别为15.8个月(95%置信区间[CI],12.5-19.0)、2.4个月(95% CI,1.2-3.6)和1.1个月(95% CI,1.0-1.2)。在化疗达到疾病控制后接受附加尼妥珠单抗治疗的患者中,在未确认疾病控制的前提下同时接受尼妥珠单抗和化疗的患者中,以及在未同时接受化疗的情况下接受尼妥珠单抗治疗的患者中,尼妥珠单抗对Tregs的影响分别为1.1(95% CI 1.0-1.2)个月、2.4(95% CI 1.2-3.6)个月和1.1(95% CI 1.0-1.2)个月:在化疗后病情得到控制的晚期PDAC患者中,加用nivolumab与OS的改善有关。
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引用次数: 0
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Cancer Immunology, Immunotherapy
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