免疫原性
肿瘤微环境
免疫系统
串扰
免疫
生物
免疫检查点
癌症研究
癌症
免疫疗法
肿瘤进展
肿瘤细胞
免疫学
作者
Yochai Wolf,Yardena Samuels
标识
DOI:10.1158/1078-0432.ccr-21-1355
摘要
Abstract Over the last decade, it has become clear that the genomic landscapes of tumors profoundly impact their immunogenicity and how tumor cells interact with immune cells. Whereas past discoveries mainly focused on the interplay between tumor immunogenicity and tumor mutational burden (TMB), under the assumption that a higher mutation load would give rise to a better patient response to immune checkpoint blockade (ICB) therapies, we and others have underlined intratumor heterogeneity (ITH) as an important determinant of the magnitude of the anti-tumor response and the nature of the tumor microenvironment. In this Review, we define TMB vs. ITH and how the two factors are being inferred from data, examine key findings in the cancer immunogenomics literature deciphering the complex crosstalk between TMB, ITH and anti-tumor immunity in human cancers and in-vivo models, and discuss the mutual influence of ITH and immunity - how the anti-tumor response can give rise to tumors with higher ITH, and how higher ITH can put shackles on the anti-tumor response.
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