Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nat Genet. 2019 Feb;51(2):202-206. doi: 10.1038/s41588-018-0312-8. Epub 2019 Jan 14.
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.
免疫检查点抑制剂（ICI）治疗对一些转移性癌症患者有效，但需要预测性生物标志物。在某些癌症类型中的发现表明，肿瘤突变负担（TMB）可能预测对 ICI 的临床反应。为了更广泛地研究这种关联，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（每种组织学中最高的 20%）与总体生存改善相关。对于大多数癌症组织学类型，观察到较高的 TMB 与生存改善之间存在关联。与生存改善相关的 TMB 切点在癌症类型之间差异很大。这些数据表明，TMB 与接受广泛各种癌症类型的 ICI 治疗的患者的生存改善相关，但可能没有一个通用的高 TMB定义。
