Tumor mutational load predicts survival after immunotherapy across multiple cancer types
Tumor mutational load predicts survival after immunotherapy across multiple cancer types
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DOI：
10.1038/s41588-018-0312-8
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发表时间：
2019-02-01
期刊：
影响因子：
30.8
通讯作者：
Morris, Luc G. T.
中科院分区：
文献类型：
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作者：
Samstein, Robert M.;Lee, Chung-Han;Morris, Luc G. T.
免疫检查点抑制(ICI)治疗使一些转移性癌症患者受益，但需要预测性生物标志物。在选定的癌症类型中的研究结果表明，肿瘤突变负荷(TMB)可能预测ICI的临床反应。为了更广泛地研究这种联系，我们分析了1662名接受ICI治疗的晚期癌症患者和5371名未接受ICI治疗的晚期癌症患者的临床和基因组数据，这些患者的肿瘤接受了靶向下一代测序(MSK-IMPACT)。在所有患者中，较高的体细胞TMB(在每种组织学中最高的20%)与更好的总体存活率相关。对于大多数癌症组织学，观察到较高的TMB与改善的存活率之间的联系。与提高存活率相关的TMB临界点在不同的癌症类型之间有显著差异。这些数据表明，在接受多种癌症类型的ICI治疗的患者中，TMB与提高存活率有关，但对高TMB可能没有一个统一的定义。
Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.