Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer

作者：Yi Xiao, Ding Ma, Shen Zhao, Chen Suo, Jinxiu Shi, Mengzhu Xue, Miao Ruan, Hai Wang, Jingjing Zhao, Qin Li, Peng Wang, Leming M. Shi, Wen-Tao Yang, Wei Chieh Huang, Xin Hu, Ke‐Da Yu, Shenglin Huang, François Bertucci, Yi‐Zhou Jiang, Zhi-Ming Shao · 发表于：Clinical Cancer Research · 年份：2019 · DOI：10.1158/1078-0432.ccr-18-3524 · 被引用次数：373 · 研究领域：Cancer Immunotherapy and Biomarkers、Immunotherapy and Immune Responses、Ferroptosis and cancer prognosis

Abstract Purpose: The tumor microenvironment has a profound impact on prognosis and immunotherapy. However, the landscape of the triple-negative breast cancer (TNBC) microenvironment has not been fully understood. Experimental Design: Using the largest original multi-omics dataset of TNBC (n = 386), we conducted an extensive immunogenomic analysis to explore the heterogeneity and prognostic significance of the TNBC microenvironment. We further analyzed the potential immune escape mechanisms of TNBC. Results: The TNBC microenvironment phenotypes were classified into three heterogeneous clusters: cluster 1, the “immune-desert” cluster, with low microenvironment cell infiltration; cluster 2, the “innate immune-inactivated” cluster, with resting innate immune cells and nonimmune stromal cells infiltration; and cluster 3, the “immune-inflamed” cluster, with abundant adaptive and innate immune cells infiltration. The clustering result was validated internally with pathologic sections and externally with The Cancer Genome Atlas and METABRIC cohorts. The microenvironment clusters had significant prognostic efficacy. In terms of potential immune escape mechanisms, cluster 1 was characterized by an incapability to attract immune cells, and MYC amplification was correlated with low immune infiltration. In cluster 2, chemotaxis but inactivation of innate immunity and low tumor antigen burden might contribute to immune escape, and mutations in the PI3K-AKT pathway might be correlated with...