干旱区生态环境知识资源中心(Arid): Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer

Arid

DOI	10.1158/1078-0432.CCR-18-3524
	Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer
	Xiao, Yi 1; Ma, Ding 1; Zhao, Shen 1; Suo, Chen 2; Shi, Jinxiu 3,4; Xue, Meng-Zhu 5; Ruan, Miao 6; Wang, Hai 1; Zhao, Jingjing 7,8; Li, Qin 7,8; Wang, Peng 9; Shi, Leming 2; Yang, Wen-Tao 6; Huang, Wei 3,4; Hu, Xin 1; Yu, Ke-Da 1; Huang, Shenglin 7,8; Bertucci, Francois 10; Jiang, Yi-Zhou 1; Shao, Zhi-Ming 1
通讯作者	Jiang, Yi-Zhou
来源期刊	CLINICAL CANCER RESEARCH
ISSN	1078-0432
EISSN	1557-3265
出版年	2019
卷号	25 期号:16 页码:5002-5014
英文摘要	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 multiomics 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 this effect. Cluster 3 featured high expression of immune checkpoint molecules. Conclusions: Our study represents a step toward personalized immunotherapy for patients with TNBC. Immune checkpoint inhibitors might be effective for immune-inflamed cluster, and the transformation of cold tumors into hot tumors should be considered for immune-desert and innate immune-inactivated clusters.
类型	Article
语种	英语
国家	Peoples R China ; France
开放获取类型	Bronze
收录类别	SCI-E
WOS记录号	WOS:000481912400018
WOS关键词	TUMOR-INFILTRATING LYMPHOCYTES ; CELLS ; IDENTIFICATION ; EXPRESSION ; LANDSCAPE ; SUBTYPES ; GROWTH
WOS类目	Oncology
WOS研究方向	Oncology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/214930
作者单位	1.Fudan Univ, Shanghai Canc Ctr, Dept Breast Surg, Shanghai, Peoples R China; 2.Fudan Univ, State Key Lab Genet Engn, Sch Life Sci & Human Phenome Inst, Shanghai, Peoples R China; 3.Chinese Natl Human Genome Ctr, Shanghai MOST Key Lab Hlth & Dis Genom, Shanghai, Peoples R China; 4.SITI, Shanghai, Peoples R China; 5.Chinese Acad Sci, Shanghai Adv Res Inst, SARI Ctr Stem Cell & Nanomed, Shanghai, Peoples R China; 6.Fudan Univ, Shanghai Canc Ctr, Dept Pathol, Shanghai, Peoples R China; 7.Fudan Univ, Shanghai Canc Ctr, Floor 8,270 Dongan Rd, Shanghai 200032, Peoples R China; 8.Fudan Univ, Inst Biomed Sci, Shanghai Med Coll, Shanghai, Peoples R China; 9.Chinese Acad Sci, Shanghai Inst Biol Sci, CAS MPG Partner Inst Computat Biol, Biomed Big Data Ctr,Key Lab Computat Biol, Shanghai, Peoples R China; 10.Inst Paoli Calmettes, Dept Med Oncol, Predict Oncol Team, CRCM, Marseille, France
推荐引用方式 GB/T 7714	Xiao, Yi,Ma, Ding,Zhao, Shen,et al. Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer[J],2019,25(16):5002-5014.
APA	Xiao, Yi.,Ma, Ding.,Zhao, Shen.,Suo, Chen.,Shi, Jinxiu.,...&Shao, Zhi-Ming.(2019).Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer.CLINICAL CANCER RESEARCH,25(16),5002-5014.
MLA	Xiao, Yi,et al."Multi-Omics Profiling Reveals Distinct Microenvironment Characterization and Suggests Immune Escape Mechanisms of Triple-Negative Breast Cancer".CLINICAL CANCER RESEARCH 25.16(2019):5002-5014.