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Prognostic Value and Immune Signatures of Anoikis-related Genes in Breast Cancer. 乳腺癌中 Anoikis 相关基因的预后价值和免疫特征
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI: 10.1097/CJI.0000000000000523
Qing Wu, Yang Luo, Nan Lin, Shiyao Zheng, Xianhe Xie

From databases of the Cancer Genome Atlas (TCGA) and GSE42568, transcriptome data of breast cancer patients was obtained. Then, anoikis-related genes (ANRGs) were identified and constructed a risk score system. As a threshold value, the median risk score was used to stratify patients into low-risk and high-risk groups. Kaplan-Meier analysis was then conducted to evaluate the prognostic ability of the risk score system, which was validated using GSE7390. Furthermore, we identified potential enrichment of function and tumor immune infiltration in the model. Finally, the biological functions of a risk gene (EPB41L4B) in breast cancer were investigated through in vitro experiments. We constructed a risk score system via 9 prognosis ANRGs (CXCL2, EPB41L4B, SLC7A5, SFRP1, SDC1, BHLHE41, SPINT1, KRT15, and CD24). The Kaplan-Meier analysis showed that both TCGA-BRCA (training set) and GSE7390 (testing set) patients with high-risk status had significantly worse survival outcomes. In addition, the calibration plots were in good agreement with the prognosis prediction. Breast cancer patients with immunosuppressive microenvironment could be screened using risk groups since risk scores were correlated negatively with ESTIMATE score, tumor-infiltration lymphocytes, immune checkpoints, and chemotactic factors. Furthermore, cellular viability and cell migration of cancerous breast cells were inhibited and apoptosis was promoted by down-regulation of EPB41L4B gene expression. Based on ANRGs, a 9-gene prognostic model could be developed to predict breast cancer prognosis; moreover, patients of the high-risk group were in an immunosuppressed tumor microenvironment.

从癌症基因组图谱(TCGA)和GSE42568数据库中获得了乳腺癌患者的转录组数据。然后,确定了乳腺癌相关基因(ANRGs),并构建了风险评分系统。以风险评分中位数作为阈值,将患者分为低风险组和高风险组。然后进行 Kaplan-Meier 分析,评估风险评分系统的预后能力,并使用 GSE7390 对其进行了验证。此外,我们还发现了模型中潜在的功能富集和肿瘤免疫浸润。最后,我们通过体外实验研究了风险基因(EPB41L4B)在乳腺癌中的生物学功能。我们通过9个预后ANRGs(CXCL2、EPB41L4B、SLC7A5、SFRP1、SDC1、BHLHE41、SPINT1、KRT15和CD24)构建了一个风险评分系统。Kaplan-Meier分析表明,TCGA-BRCA(训练集)和GSE7390(测试集)高危患者的生存结果都明显较差。此外,校准图与预后预测结果十分吻合。由于风险评分与ESTIMATE评分、肿瘤浸润淋巴细胞、免疫检查点和趋化因子呈负相关,因此可以利用风险组来筛选具有免疫抑制微环境的乳腺癌患者。此外,下调 EPB41L4B 基因的表达可抑制乳腺癌细胞的活力和迁移,并促进细胞凋亡。基于ANRGs,可以建立一个9基因预后模型来预测乳腺癌的预后;此外,高风险组患者处于免疫抑制的肿瘤微环境中。
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引用次数: 0
Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics. 关于转移性滑膜肉瘤中 MAGE-A4 和癌症睾丸抗原共表达的简要交流:开发免疫疗法的考虑因素。
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-03 DOI: 10.1097/CJI.0000000000000541
Hélène Vanacker, Robert Connacher, Alexandra Meurgey, Julien Bollard, Valéry Attignon, Franck Tirode, Myriam Jean-Denis, Mehdi Brahmi, Jean-Yves Blay, Ruoxi Wang, Dennis Williams, Armelle Dufresne

Therapeutic options for synovial sarcoma (SyS) have not evolved for several decades and the efficacy of second-line treatments is very limited. The expression of a large family of proteins known as cancer testis antigens (CTAs) in SyS has spurred the development of targeted T-cell therapies currently in clinical trials, such as those aimed at melanoma-associated antigen (MAGE)-A4 and New York esophageal squamous cell carcinoma 1 (NY-ESO-1), which have shown promising clinical efficacy. Extensive knowledge of the prevalence of expression and coexpression of CTAs is critical to design T-cell therapies with optimal coverage of the patient population. We analyzed the expression of CTAs of the MAGE-A family as well as NY-ESO-1 and preferentially expressed antigen in melanoma (PRAME) by RNA sequencing in a large cohort of 133 SyS samples from patients registered in the French sarcoma database (NETSARC+). Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%). Almost all samples (92%) expressing any of the MAGE-As also expressed MAGE-A4. NY-ESO-1 was expressed in 65% of samples, with a large but incomplete overlap with MAGE-A4, whereas PRAME was present in 121 (91%) samples. Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.

几十年来,滑膜肉瘤(SyS)的治疗方案一直没有发展,二线治疗的疗效也非常有限。在滑膜肉瘤中表达的一大类蛋白被称为癌睾丸抗原(CTA),这促进了目前正在进行临床试验的靶向 T 细胞疗法的发展,例如针对黑色素瘤相关抗原(MAGE)-A4 和纽约食管鳞状细胞癌 1(NY-ESO-1)的疗法,这些疗法已显示出良好的临床疗效。广泛了解CTAs的表达和共表达的普遍性,对于设计出最佳覆盖患者人群的T细胞疗法至关重要。我们通过 RNA 测序分析了法国肉瘤数据库(NETSARC+)中登记的 133 例 SyS 患者样本中 MAGE-A 家族 CTAs 以及 NY-ESO-1 和黑色素瘤优先表达抗原(PRAME)的表达情况。在MAGE-As中,MAGE-A4的流行率最高(65%),其次是MAGE-A10(15%)和MAGE-A9(13%)。几乎所有表达任何一种 MAGE-As 的样本(92%)都同时表达 MAGE-A4。65%的样本表达 NY-ESO-1,与 MAGE-A4 有大量重叠,但不完全重叠,而 121 个样本(91%)中存在 PRAME。互补免疫组化分析用于确定 MAGE-A4 和 NY-ESO-1 的 RNA 和蛋白质表达之间的正相关性。这些数据为T细胞疗法在SyS患者中的最佳覆盖策略提供了信息,为SyS患者提供了单线或联合二线治疗的新选择。
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引用次数: 0
Multiomics Analysis of Interleukin-21 as a Potential Immunologic and Biomarker in Hepatocellular Carcinoma. 白细胞介素-21作为肝细胞癌潜在免疫学和生物标记物的多组学分析
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-04 DOI: 10.1097/CJI.0000000000000526
Yonghui Ma, Guanming Shao, Yuwei Xie, Dongxia Yang, Kun Li, Bin Tan, Cong Wang, Peng Sun, Jingyu Cao

Interleukin-21 (IL-21) is an important antitumor cytokine that contributes to the proliferation and differentiation of CD8 + T cells. It has been proven to enhance the response to immune checkpoint inhibitors (ICIs) in various solid tumors. However, its role in hepatocellular carcinoma (HCC) has not yet been clarified. In this research, we aimed to investigate the antitumor effect of IL-21 in HCC and its effect on ICI treatment. Through transcriptome sequencing analysis and immunohistochemistry validation, we found that patients with high IL-21 expression had a better prognosis. HCCs with high expression of IL-21 had higher infiltration of CD8 + T cells, increased expression of immune checkpoints, and an improved response to ICI treatment. In conclusion, IL-21 can enhance the efficacy of ICI treatment and improve the prognosis of patients by promoting the infiltration of CD8 + T cells and the expression of immune checkpoint-related genes.

白细胞介素-21(IL-21)是一种重要的抗肿瘤细胞因子,有助于 CD8+ T 细胞的增殖和分化。事实证明,它能增强各种实体瘤对免疫检查点抑制剂(ICIs)的反应。然而,它在肝细胞癌(HCC)中的作用尚未明确。本研究旨在探讨IL-21在HCC中的抗肿瘤作用及其对ICI治疗的影响。通过转录组测序分析和免疫组化验证,我们发现IL-21高表达的患者预后较好。IL-21 高表达的 HCC 有更高的 CD8+ T 细胞浸润,免疫检查点表达增加,对 ICI 治疗的反应也有所改善。总之,IL-21能促进CD8+ T细胞浸润和免疫检查点相关基因的表达,从而提高ICI治疗的疗效,改善患者的预后。
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引用次数: 0
A Synthetic Circuit Empowering Reprogrammed B Cells for Therapeutic Proteins Expression Regulated by Tumor Detection. 一种通过肿瘤检测调控重编程 B 细胞表达治疗蛋白的合成电路。
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-22 DOI: 10.1097/CJI.0000000000000524
Audrey Page, Marie Delles, Didier Nègre, Caroline Costa, Floriane Fusil, François-Loïc Cosset

Cancer remains a leading cause of death worldwide, but immunotherapies hold promises to cure it by awaking the patient's immune system to provide long-term protection. Cell therapies, involving the infusion of immune cells, either directly or genetically modified, are being developed to recognize and destroy cancer cells. Here, we explored the potential of a new synthetic circuit to reprogram B cells to cure cancers. This circuit consists in a sensor (a membrane-anchored IgG1), a transducer (a fragment of the NR4A1 promoter) and an effector molecule. Upon recognition of its target, this sensor triggers signaling pathways leading to the activation of the transducer and to effector expression (here, a reporter molecule). We showed that this circuit could discriminate tumors expressing the target antigen from those that did not, in a dose dependent manner in vitro. Going further, we replaced the original membrane-anchored sensor by an immunoglobulin expression cassette that can not only be membrane-anchored but also be secreted depending on B-cell maturation status. This allowed concomitant activation of the circuit and secretion of transgenic antibodies directed against the targeted antigen. Of note, these antibodies could correctly bind their target and were recognized by FcR expressed at the surface of immune cells, which should synergically amplify the action of the effector. The potential of reprogrammed B cells remains to be assessed in vivo by implementing a therapeutic effector. In the future, B-cell reprogramming platforms should allow personalized cancer treatment by adapting both the sensor and the therapeutic effectors to patients.

癌症仍然是全球死亡的主要原因,但免疫疗法有望通过唤醒病人的免疫系统来提供长期保护,从而治愈癌症。目前正在开发的细胞疗法涉及直接或经基因修饰的免疫细胞输注,以识别和摧毁癌细胞。在这里,我们探索了一种新的合成电路的潜力,以重新编程 B 细胞来治疗癌症。该回路由传感器(膜锚定 IgG1)、转换器(NR4A1 启动子片段)和效应分子组成。一旦识别到目标,传感器就会触发信号通路,从而激活转导因子并表达效应分子(这里是一个报告分子)。我们的研究表明,在体外,这种回路能以剂量依赖的方式区分表达靶抗原的肿瘤和不表达靶抗原的肿瘤。此外,我们还用免疫球蛋白表达盒取代了原来的膜锚定传感器,该表达盒不仅可以膜锚定,还可以根据 B 细胞成熟状态分泌。这样就能同时激活电路和分泌针对目标抗原的转基因抗体。值得注意的是,这些抗体可以正确地与目标结合,并被免疫细胞表面表达的 FcR 识别,从而协同放大效应物的作用。重编程 B 细胞的潜力还有待通过治疗效应物在体内进行评估。未来,B 细胞重编程平台应能根据患者的情况调整传感器和治疗效应器,从而实现个性化癌症治疗。
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引用次数: 0
Identification of the CD8 + T-cell Related Signature for Predicting the Prognosis of Gastric Cancer Based on Integrated Analysis of Bulk and Single-cell RNA Sequencing Data. 基于批量和单细胞 RNA 测序数据的综合分析,确定预测胃癌预后的 CD8+ T 细胞相关特征。
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-29 DOI: 10.1097/CJI.0000000000000528
Zhi-Gang Zhu, Zheng Wang, Qiong Wu, Dong-Liu Miao, Yi-Qi Jin, Lei Chen

The infiltration of CD8 + T cells in the tumor microenvironment is associated with better survival and immunotherapy response. However, their roles in gastric cancer have not been explored so far. In here, the profiles of GC gene expression were collected from The Cancer Genome Atlas database. Single-cell transcriptomic data originated from GSE134520. Cell clustering, annotation, and CD8 + T-cell differential genes were from the TISCH database. We determined 896 CD8 + T-cell differential genes by scRNA-seq analysis. After integrating immune-related genes, 174 overlapping genes were obtained and a novel risk model was subsequently built. The performance of CD8 + T-cell-associated gene signature was assessed in the training and external validation sets. The gene signature showed independent risk factors of overall survival for GC. A quantitative nomogram was built to enhance the clinical efficacy of this signature. Furthermore, low-risk individuals showed higher mutation status, higher immune checkpoint expression, low Tumour Immune Dysfunction and Exclusion (TIDE) scores, and higher IPS-PD-1 combined IPS-CTLA4 scores, indicating a greater response to immunotherapy. In addition, analysis of IMvigor210 immunotherapy cohort demonstrated that low-risk individuals had a favorable response to prognosis and immunotherapy. In conclusion, we generated a CD8 + T-cell-related signature that can serve as a promising tool for personalized prognosis prediction and guiding decisions regarding immunotherapy in GC patients.

肿瘤微环境中的 CD8+ T 细胞浸润与更好的生存和免疫治疗反应有关。然而,迄今为止,它们在胃癌中的作用尚未得到探讨。本文从癌症基因组图谱数据库中收集了胃癌基因表达谱。单细胞转录组数据来自 GSE134520。细胞聚类、注释和CD8+ T细胞差异基因来自TISCH数据库。我们通过 scRNA-seq 分析确定了 896 个 CD8+ T 细胞差异基因。整合免疫相关基因后,得到了174个重叠基因,随后建立了一个新的风险模型。在训练集和外部验证集中评估了 CD8+ T 细胞相关基因特征的性能。基因特征显示了GC总生存率的独立风险因素。建立的定量提名图提高了该特征的临床疗效。此外,低风险个体表现出更高的突变状态、更高的免疫检查点表达、较低的肿瘤免疫功能障碍和排斥(TIDE)评分以及更高的IPS-PD-1联合IPS-CTLA4评分,这表明他们对免疫疗法的反应更大。此外,对IMvigor210免疫疗法队列的分析表明,低风险个体对预后和免疫疗法的反应良好。总之,我们生成的 CD8+ T 细胞相关特征可作为一种有前途的工具,用于 GC 患者的个性化预后预测和免疫治疗决策指导。
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引用次数: 0
Bronchiolitis after Combination Immunotherapy With Ipilimumab and Nivolumab in a Melanoma Patient. 一名黑色素瘤患者接受伊匹单抗和尼伐单抗联合免疫疗法后出现支气管炎。
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-02-27 DOI: 10.1097/CJI.0000000000000509
Shahir Basir, Jana Bosiers, Hans M Westgeest, David C Y Yick, Jochem R van Werven, Cor H van der Leest

Therapy with immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of metastatic melanoma but is also associated with various immune-related adverse events (AE), including pulmonary toxicity. Herein, we describe the case of a 60-year-old female with metastasized melanoma with BRAF mutation under combination immunotherapy with ipilimumab and nivolumab, who presented with a persistent, nonproductive cough for the last two months. Her CT-scan showed de novo bronchial inflammation and wall thickening in all lung fields. Initial treatment with antimicrobial treatment and inhalation corticosteroids did not resolve her symptoms, nor the radiologic abnormalities. Additional testing with transbronchial cryobiopsy showed a histologic picture of diffuse ill-formed granulomas and the presence of moderate chronic active inflammation of the respiratory epithelium, consistent with medication-related bronchiolitis. Bronchiolitis, as present in this case, has rarely been reported as an immune-related AE. A thorough diagnostic workup is mandatory as it remains a diagnosis of exclusion. Management consists of discontinuing ICIs and administering systemic corticosteroids. The addition of immunosuppressive agents (e, infliximab, cyclophosphamide, or mycophenolate mofetil) can be considered in refractory cases. In our case, clinical and radiologic resolution was achieved after discontinuing the ICI and treatment with high-dose prednisone. This case shows that although bronchiolitis is a rare immune-related side effect of ICIs, oncologists, and pulmonologists should always be aware of this relatively easily treatable AE.

免疫检查点抑制剂(ICIs)的治疗显著改善了转移性黑色素瘤的预后,但也与各种免疫相关不良事件(AE)有关,包括肺毒性。在此,我们描述了一例60岁女性患者的病例,她患有BRAF突变的转移性黑色素瘤,正在接受伊匹单抗和尼伐单抗的联合免疫治疗。CT扫描显示她的支气管有新的炎症,所有肺野的支气管壁增厚。最初采用抗菌治疗和吸入皮质类固醇治疗并没有缓解她的症状,也没有发现放射学异常。经支气管冷冻活组织切片的进一步检查显示,组织学图像为弥漫性不规则肉芽肿,呼吸道上皮存在中度慢性活动性炎症,与药物相关性支气管炎一致。本病例中出现的支气管炎很少被报告为免疫相关的急性呼吸道感染。由于该病仍属于排除性诊断,因此必须进行彻底的诊断检查。治疗包括停用 ICIs 和使用全身性皮质类固醇。对于难治性病例,可考虑添加免疫抑制剂(如英夫利昔单抗、环磷酰胺或霉酚酸酯)。在我们的病例中,在停用 ICI 和大剂量泼尼松治疗后,临床和放射学症状均得到缓解。本病例表明,虽然支气管炎是 ICIs 罕见的免疫相关副作用,但肿瘤学家和肺科专家应始终注意这种相对容易治疗的 AE。
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引用次数: 0
Survival Impact of Inflammation-based Prognostic Scores in Metastatic or Unresectable Esophageal Cancer Treated With Pembrolizumab Plus Chemotherapy. 基于炎症的预后评分对使用 Pembrolizumab 加化疗治疗的转移性或无法切除的食管癌患者生存期的影响
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-06-03 DOI: 10.1097/CJI.0000000000000529
Takahito Sugase, Takashi Kanemura, Tomohira Takeoka, Norihiro Matsuura, Yasunori Masuike, Naoki Shinno, Hisashi Hara, Masatoshi Kitakaze, Masahiko Kubo, Yosuke Mukai, Toshinori Sueda, Shinichiro Hasegawa, Hirofumi Akita, Junichi Nishimura, Hiroshi Wada, Masayoshi Yasui, Takeshi Omori, Hiroshi Miyata

Pembrolizumab plus chemotherapy has been indicated as the first-line treatment for metastatic or unresectable locally advanced esophageal cancer. However, pretreatment biomarkers for predicting clinical outcomes remain unclear. We investigated the predictive value of inflammation-based prognostic scores in patients treated with pembrolizumab and chemotherapy. The Prognostic Nutritional Index (PNI), C-reactive protein/albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were calculated before initial treatment in 65 eligible patients with metastatic or unresectable locally advanced esophageal cancer receiving pembrolizumab plus CF therapy, and the relationship between these biomarkers and clinical outcomes was analyzed. The objective response rate (ORR) and progression disease (PD) were observed in 51% and 21% of all patients. Patients with PNI<39 have significantly worse treatment responses than those with PNI≥39 (ORR; 28% vs. 60%, PD; 44% vs. 13%, P =0.020). Progression-free survival (PFS) is significantly associated with the PNI and CAR ( P <0.001 and P =0.004, respectively). Overall survival (OS) is associated with PNI, CAR, and PLR ( P <0.001, P =0.008, and P =0.018, respectively). The PNI cutoff value of 39 is identified as an independent factor for PFS (odds ratio=0.27, 95% CI: 0.18-0.81, P =0.012) and OS (odds ratio=0.22, 95% CI: 0.08-0.59, P =0.003). Patients with PNI<39 have significantly worse 6-month PFS and 1-year OS than those with PNI≥39 (27.8% vs. 66.7%, 27.2% vs. 81.1%, respectively). In conclusion, inflammation-based prognostic scores are associated with survival in patients treated with pembrolizumab plus CF therapy. Pretreatment PNI is a promising candidate for predicting treatment response and survival.

Pembrolizumab 联合化疗已被列为转移性或无法切除的局部晚期食管癌的一线治疗方法。然而,预测临床结果的预处理生物标志物仍不明确。我们研究了基于炎症的预后评分对接受彭博利珠单抗和化疗患者的预测价值。我们在65名接受pembrolizumab加CF治疗的符合条件的转移性或无法切除的局部晚期食管癌患者的初始治疗前计算了预后营养指数(PNI)、C反应蛋白/白蛋白比值(CAR)、中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR),并分析了这些生物标志物与临床预后之间的关系。在所有患者中,分别有51%和21%的患者观察到了客观反应率(ORR)和疾病进展(PD)。PNI患者
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引用次数: 0
False-positive Findings of Large Vessel Vasculitis on FDG-PET in Patients Treated With Immune Checkpoint Inhibitors. 免疫检查点抑制剂治疗患者的 FDG-PET 大血管炎假阳性发现
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-20 DOI: 10.1097/CJI.0000000000000527
Dylan Johnson, Shahin Jamal, Ryan W Hung, Carrie Ye

Fluorine-18 fluorodeoxygluocose positron emission tomography (FDG-PET) is increasingly used in the evaluation of response to immune checkpoint inhibitor (ICI) therapy. Incidental findings of increased vessel wall uptake may prompt the concern for ICI-induced large vessel vasculitis (LVV). Precise radiographic and clinical evaluation is required to determine if this represents true vasculitis, as use of immune suppression and ICI discontinuation can have significant impacts on patient outcomes. We performed a retrospective case analysis of 4 consecutive patients referred to 2 rheumatology clinics treated with ICI with incidental findings of LVV on FDG-PET, reviewing their clinical course and radiographic findings. All 4 cases had FDG-PET scans for routine oncology indications and had no associated clinical features of LVV. One patient was treated with corticosteroids and no patients developed any clinical evidence of vasculitis during a mean follow-up period of 17 months (range: 7-33 mo). All FDG-PET images reporting LVV underwent a standardized analysis to identify any technical issues or concerns with interpretation. In review of imaging, 3 of the cases may have been due to delayed tracer to scan interval leading to misinterpretation of vascular uptake as suspected LVV. Recognition of technical pitfalls in FDG-PET interpretation is crucial to inform the need for immunosuppression and the safety of continued ICI therapy.

氟-18-脱氧葡萄糖正电子发射断层扫描(FDG-PET)越来越多地用于评估免疫检查点抑制剂(ICI)疗法的反应。偶然发现的血管壁摄取增加可能会引发对 ICI 诱导的大血管炎(LVV)的担忧。由于使用免疫抑制剂和停用 ICI 会对患者预后产生重大影响,因此需要进行精确的放射学和临床评估,以确定这是否代表真正的血管炎。我们对转诊至两家风湿病诊所接受 ICI 治疗并在 FDG-PET 上偶然发现 LVV 的 4 例连续患者进行了回顾性病例分析,回顾了他们的临床病程和影像学检查结果。这4例患者都是因常规肿瘤适应症而进行FDG-PET扫描,没有相关的左心室静脉瘤临床特征。一名患者接受了皮质类固醇治疗,在平均 17 个月(7-33 个月)的随访期间,没有患者出现任何血管炎的临床症状。所有报告左心室积液的 FDG-PET 图像都经过了标准化分析,以确定任何技术问题或解释问题。在对成像进行复查时,有 3 例病例可能是由于示踪剂与扫描时间间隔延迟,导致血管摄取被误认为是疑似左心室变性。识别 FDG-PET 解读中的技术误区对于确定免疫抑制的必要性和继续 ICI 治疗的安全性至关重要。
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引用次数: 0
Nivolumab as a Promising Treatment Option for Metastatic Salivary Duct Carcinoma. Nivolumab是治疗转移性唾液腺导管癌的一种很有前途的方法。
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-28 DOI: 10.1097/CJI.0000000000000513
Luis Bugia, Frederic Jungbauer, Lena Zaubitzer, Christian Hörner, Kirsten Merx, Abo-Madyan Yasser, Thomas Germann, Anne Lammert, Claudia Scherl, Nicole Rotter, Annette Affolter

Salivary duct carcinomas (SDC) of the parotid gland are rarely occurring highly malignant tumors. A 65-year-old man presented with a preauricular mass. After surgical treatment and histologic examination, the findings were interpreted as a squamous cell carcinoma (SCC) metastasis of the parotid gland deriving from a cancer of unknown primary DD primary SCC of the parotid gland. Adjuvant platinum-based radiochemotherapy was administered in domo. However, re-staging revealed multiple size-progressive pulmonary round lesions. After resection and histological examination of a pulmonary mass and in synopsis with the primary tumor, the initial diagnosis of SCC was revised to SDC of the parotid gland. With positive HER-2 status, off-label trastuzumab/docetaxel was initiated in an individual healing attempt, during which the pulmonary metastases showed clear progression. Consequently, the patient received immunotherapy with nivolumab according to his negative PD-L1 status. After 57 cycles of nivolumab, the patient presents with partial remission and in good condition. We report, for the first time, a robust response of metastatic SDC to checkpoint inhibition with nivolumab without additional radiotherapy.

腮腺唾液腺导管癌(SDC)是一种罕见的高度恶性肿瘤。一名 65 岁的男子出现耳前肿块。经过手术治疗和组织学检查,结果被解释为腮腺鳞状细胞癌(SCC)转移瘤,来源于原发性不明的腮腺原发性 SCC。患者接受了以铂为基础的辅助放化疗。然而,重新分期后发现了多个大小呈进行性发展的肺圆形病灶。在对肺部肿块进行切除和组织学检查并与原发肿瘤进行对比后,最初的 SCC 诊断被修改为腮腺 SDC。由于患者的 HER-2 状态为阳性,在一次个体治疗尝试中,患者接受了标签外曲妥珠单抗/多西他赛治疗,在此期间,肺转移灶出现了明显的进展。因此,患者根据其 PD-L1 阴性状态接受了 nivolumab 免疫疗法。经过 57 个周期的尼夫单抗治疗后,患者病情得到部分缓解,目前状况良好。我们首次报道了转移性 SDC 对使用 nivolumab 的检查点抑制剂的强效反应,而无需额外的放疗。
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引用次数: 0
Single-cell RNA Sequencing Analysis Reveals Cancer-associated Fibroblast Signature for Prediction of Clinical Outcomes and Immunotherapy in Gastric Cancer. 单细胞 RNA 测序分析揭示癌症相关成纤维细胞特征,用于预测胃癌的临床结果和免疫疗法
IF 3.2 4区 医学 Q3 IMMUNOLOGY Pub Date : 2024-08-29 DOI: 10.1097/CJI.0000000000000539
Xiaoxiao Li, Bo Tang, Ouyang Yujie, Chuan Xu, Shuanghu Yuan

Gastric cancer (GC) is a significant worldwide health concern and is a leading cause of cancer-related mortality. Immunotherapy has arisen as a promising strategy to stimulate the patient's immune system in combating cancer cells. Nevertheless, the effectiveness of immunotherapy in individuals with gastric cancer (GC) is not yet optimal. Thus, it is crucial to discover biomarkers capable appof predicting the advantages of immunotherapy for tailored treatment. The tumor microenvironment (TME) and its constituents, including cancer-associated fibroblasts (CAFs), exert a substantial influence on immune responses and treatment outcomes. In this investigation, we utilized single-cell RNA sequencing to profile CAFs in GC and established a scoring method, referred to as the CAF score (CAFS), for the prediction of patient prognosis and response to immunotherapy. Through our analysis, we successfully identified distinct subgroups within CAFs based on CAF score (CAFS), namely CAFS-high and CAFS-low subgroups. Notably, we noted that individuals within the CAFS-high subgroup experienced a lessF favorable prognosis and displayed diminished responsiveness to immunotherapy in contrast to the CAFS low subgroup. Furthermore, we analyzed the mutation and immune characteristics of these subgroups, identifying differentially mutated genes and immune cell compositions. We established that CAFS could forecast treatment advantages in patients with gastric cancer, both for chemotherapy and immunotherapy. Its efficacy was additionally confirmed in contrast to other biomarkers, including Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenotypic Score (IPS). These findings emphasize the clinical relevance and potential utility of CAFS in guiding personalized treatment strategies for gastric cancer.

胃癌(GC)是全球关注的重大健康问题,也是癌症相关死亡的主要原因。免疫疗法是刺激患者免疫系统对抗癌细胞的一种有前途的策略。然而,免疫疗法对胃癌患者的疗效尚不理想。因此,发现能够预测免疫疗法优势的生物标志物以进行有针对性的治疗至关重要。肿瘤微环境(TME)及其组成成分,包括癌症相关成纤维细胞(CAFs),对免疫反应和治疗效果有很大影响。在这项研究中,我们利用单细胞 RNA 测序分析了 GC 中的 CAFs,并建立了一种称为 CAF 评分(CAFS)的评分方法,用于预测患者的预后和对免疫疗法的反应。通过分析,我们成功地根据 CAF 评分(CAFS)在 CAFs 中识别出了不同的亚组,即 CAFS 高亚组和 CAFS 低亚组。值得注意的是,与 CAFS 低亚组相比,CAFS 高亚组中的个体预后较差,对免疫疗法的反应性也较弱。此外,我们还分析了这些亚组的突变和免疫特征,确定了不同的突变基因和免疫细胞组成。我们发现,CAFS 可以预测胃癌患者在化疗和免疫治疗方面的治疗优势。与其他生物标记物(包括肿瘤免疫功能障碍和排斥(TIDE)和免疫表型评分(IPS))相比,CAFS 的疗效得到了进一步证实。这些发现强调了 CAFS 在指导胃癌个性化治疗策略方面的临床意义和潜在作用。
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Journal of Immunotherapy
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