The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing 210008, PR China.
Future Oncol. 2020 Mar;16(9):469-481. doi: 10.2217/fon-2019-0650. Epub 2020 Feb 12.
Immunocheckpoint inhibitors (ICIs) which target and CTLA-4 have dramatically changed the history of non-small-cell lung cancer treatment. Multiple biomarkers especially tumor mutational burden (TMB) have been raised to be potential predictors of response to ICIs. However, great value of TMB has been observed in patients who receive ICIs monotherapy instead of ICIs combination therapy from latest exploratory studies. Thus, the innovative concept of TMB needs to be identified. This study uncovers specific aspects of TMB including signatures of TMB, factors related with variation, racial differences, heterogeneity between tissue TMB and blood-based TMB. Additionally, more and more factors are found valuable in clinical trials, suggesting that more markers should be further investigated as interesting candidates for response prediction beyond TMB.
免疫检查点抑制剂（ICIs）针对 PD-1 和 CTLA-4，极大地改变了非小细胞肺癌的治疗历史。多种生物标志物，特别是肿瘤突变负担（TMB），已被提出作为对 ICI 反应的潜在预测因子。然而，从最新的探索性研究来看，TMB 在接受 ICI 单药治疗的患者中具有更大的价值，而不是在接受 ICI 联合治疗的患者中。因此，需要确定 TMB 的创新概念。本研究揭示了 TMB 的具体方面，包括 TMB 的特征、与变化相关的因素、种族差异、组织 TMB 和基于血液的 TMB 之间的异质性。此外，越来越多的因素在临床试验中被证明具有价值，这表明应该进一步研究更多的标志物，作为 TMB 以外的预测反应的候选标志物。
