Immune checkpoint inhibition (ICI) has revolutionized cancer treatment, and produced durable responses in many cancer types. However, there remains a subset of patients that do not respond despite their tumors exhibiting PD-L1 expression, which highlights the need for additional biomarkers relevant to response. Here, we review checkpoint inhibitor signal pathways, resistance and sensitivity mechanisms, as well as response rates. We also investigate the correlation and response to ICI with BRCA1/2 mutation status and homologous recombination deficient tumors. Collectively we show that the use of tumor mutational burden may be effective as an emerging biomarker.

中文翻译：

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TMB：一种有前途的免疫反应生物标志物，是推进靶向治疗试验的潜在先锋。

免疫检查点抑制 (ICI) 彻底改变了癌症治疗，并在许多癌症类型中产生了持久的反应。然而，尽管肿瘤表现出 PD-L1 表达，但仍有一部分患者没有反应，这突出了对与反应相关的额外生物标志物的需求。在这里，我们回顾了检查点抑制剂信号通路、耐药性和敏感性机制，以及反应率。我们还研究了 ICI 与 BRCA1/2 突变状态和同源重组缺陷肿瘤的相关性和反应。我们共同表明，使用肿瘤突变负荷可能是一种有效的新兴生物标志物。