Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses

被引:76
作者
Chen, Yu-Pei [1 ]
Lv, Jia-Wei [1 ]
Mao, Yan-Ping [1 ]
Li, Xiao-Min [1 ]
Li, Jun-Yan [1 ]
Wang, Ya-Qin [1 ]
Xu, Cheng [1 ]
Li, Ying-Qin [1 ]
He, Qing-Mei [1 ]
Yang, Xiao-Jing [1 ]
Lei, Yuan [1 ]
Shen, Jia-Yi [1 ]
Tang, Ling-Long [1 ]
Chen, Lei [1 ]
Zhou, Guan-Qun [1 ]
Li, Wen-Fei [1 ]
Du, Xiao-Jing [1 ]
Guo, Rui [1 ]
Liu, Xu [1 ]
Zhang, Yuan [1 ]
Zeng, Jing [2 ]
Yun, Jing-Ping [2 ]
Sun, Ying [1 ]
Liu, Na [1 ]
Ma, Jun [1 ]
机构
[1] Sun Yat Sen Univ, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, State Key Lab Oncol South China, Dept Radiat Oncol,Canc Ctr,Collaborat Innovat Ctr, Guangzhou 510060, Peoples R China
[2] Sun Yat Sen Univ, Guangdong Key Lab Nasopharyngeal Carcinoma Diag &, State Key Lab Oncol South China, Dept Pathol,Canc Ctr,Collaborat Innovat Ctr Canc, Guangzhou 510060, Peoples R China
基金
中国国家自然科学基金;
关键词
Nasopharyngeal carcinoma; Tumour microenvironment; Gene expression profiles; Virtual microdissection; Prognosis; Immunotherapy responses;
D O I
10.1186/s12943-020-01292-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Currently, there is no strong evidence of the well-established biomarkers for immune checkpoint inhibitors (ICIs) in nasopharyngeal carcinoma (NPC). Here, we aimed to reveal the heterogeneity of tumour microenvironment (TME) through virtual microdissection of gene expression profiles. An immune-enriched subtype was identified in 38% (43/113) of patients, which was characterized by significant enrichment of immune cells or immune responses. The remaining patients were therefore classified as a non-Immune Subtype (non-IS), which exhibited highly proliferative features. Then we identified a tumour immune evasion state within the immune-enriched subtype (18/43, 42%), in which high expression of exclusion- and dysfunction-related signatures was observed. These subgroups were designated the Evaded and Active Immune Subtype (E-IS and A-IS), respectively. We further demonstrated that A-IS predicted favourable survival and improved ICI response as compared to E-IS and non-IS. In summary, this study introduces the novel immune subtypes and demonstrates their feasibility in tailoring immunotherapeutic strategies.
引用
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页数:8
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