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

Molecular Cancer

Jing-Ping Yun¹  Jing Zeng¹  Lei Chen²  Ying-Qin Li²  Na Liu²  Cheng Xu²  Yan-Ping Mao²  Jia-Wei Lv²  Ling-Long Tang²  Jun Ma²  Xiao-Min Li²  Ya-Qin Wang²  Jia-Yi Shen²  Xiao-Jing Du²  Jun-Yan Li²  Xiao-Jing Yang²  Ying Sun²  Yu-Pei Chen²  Yuan Zhang²  Guan-Qun Zhou²  Rui Guo²  Yuan Lei²  Qing-Mei He²  Wen-Fei Li²  Xu Liu² 

[1] Department of Pathology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy;Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy;

关键词: Nasopharyngeal carcinoma;    Tumour microenvironment;    Gene expression profiles;    Virtual microdissection;    Prognosis;    Immunotherapy responses;   

DOI  :  10.1186/s12943-020-01292-5

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown