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单细胞荟萃分析揭示了肿瘤反应性CXCL13+ T细胞对免疫检查点阻断的反应

原文发布日期：2022-09-22

英文摘要：

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单细胞荟萃分析揭示了肿瘤反应性CXCL13+ T细胞对免疫检查点阻断的反应

Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade

原文发布日期：2022-09-22

英文摘要：

Immune-checkpoint blockade (ICB) therapies represent a paradigm shift in the treatment of human cancers; however, it remains incompletely understood how tumor-reactive T cells respond to ICB across tumor types. Here, we demonstrate that measuring CXCL13 expression could effectively identify both precursor and terminally differentiated tumor-reactive CD8+ T cells within tumors. Applying this approach, we performed meta-analyses of published single-cell data for CXCL13+CD8+ T cells in 225 samples from 102 patients treated with ICB across five cancer types. We found that CXCL13+CD8+ T cells were correlated with favorable responses to ICB, and the treatment further increased such cells in responsive tumors. In addition, CXCL13+ tumor-reactive subsets exhibited variable responses to ICB in distinct contexts, likely due to different degrees of exhaustion-related immunosuppression. Our integrated analyses provide insights into mechanisms underlying ICB and suggest that bolstering precursor tumor-reactive CD8+ T cells might provide an effective therapeutic approach to improve cancer treatment.

摘要翻译：

免疫检查点阻断疗法(ICB)代表了治疗人类癌症的一种范式转变；然而， tumor-reactive T cells 在不同肿瘤类型中对ICB的反应尚不清楚。在此研究中，我们证明通过测量CXCL13的表达可以有效识别肿瘤中的前驱和终末分化肿瘤反应性CD8+ T细胞。我们将这一方法应用于ICB治疗102名患者的225份单细胞数据分析meta分析，这些样本来自5种癌症类型。我们发现CXCL13+CD8+ T细胞与对ICB治疗有利的反应相关联，并且治疗会进一步增加响应性肿瘤中的此类细胞。此外，CXCL13+的肿瘤反应性亚群在不同背景下对ICB的反应存在差异，这可能与 exhaustion 相关的免疫抑制作用的程度有关。我们整合分析的结果有助于阐明ICB的作用机制，并建议增强前驱肿瘤反应性CD8+ T细胞数量可能为改善癌症治疗提供一种有效的方法。