Pub Date : 2018-09-01DOI: 10.1158/1557-3265.AACRIASLC18-IA20
D. Carbone, Michael F. Sharpnack, K. He
Immunotherapy approaches targeting the PD-1 pathway have shown some clinical benefits in a fraction of patients with lung cancer, but expression of PD-L1 has proved to be an imperfect biomarker of efficacy. Recent studies have shown that tumor mutation burden (TMB) is also correlated with outcome and that it appears to be independent of PD-L1. TMB, however, only indirectly measures the number of neoantigenic peptides presented on tumor cell surface class I MHC, and predicted MHC matches may be an even better predictor of benefit. In addition, mutations in genes such as LKB1 may modulate the immune response, and mutations in the antigen presentation pathway may block it altogether. Mutations in DNA repair pathway genes may increase the number of potential neoantigens. Analysis of non-PD-1 pathway immunomodulators, immune cell infiltration, microenvironmental and microbiomic context, together with in-depth analysis of tumor somatic genomics, could lead to better patient selection for immunotherapy. Citation Format: David P. Carbone, Michael Sharpnack, Kai He. Immunotherapy: Biomarkers and checkpoint blockade in NSCLC [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA20.
针对PD-1途径的免疫治疗方法在部分肺癌患者中显示出一些临床益处，但PD-L1的表达已被证明是疗效的不完美生物标志物。最近的研究表明，肿瘤突变负荷(tumor mutation burden, TMB)也与预后相关，并且似乎与PD-L1无关。然而，TMB只能间接测量肿瘤细胞表面I类MHC上呈现的新抗原肽的数量，而预测的MHC匹配可能是更好的疗效预测指标。此外，LKB1等基因的突变可能调节免疫反应，抗原递呈途径的突变可能完全阻断免疫反应。DNA修复途径基因的突变可能增加潜在新抗原的数量。分析非pd -1通路免疫调节剂、免疫细胞浸润、微环境和微生物背景，以及深入分析肿瘤体细胞基因组学，可以更好地选择患者进行免疫治疗。引用格式:David P. Carbone, Michael Sharpnack, Kai He。免疫治疗:非小细胞肺癌的生物标志物和检查点阻断[摘要]。第五届AACR-IASLC国际联合会议论文集:肺癌转化科学从实验室到临床;2018年1月8日至11日;费城(PA): AACR;临床肿瘤学杂志，2018;24(增刊):1 - 12。
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