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

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.

SUBMITTER: Chen YP

PROVIDER: S-EPMC7798236 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Chen Yu-Pei YP Lv Jia-Wei JW Mao Yan-Ping YP Li Xiao-Min XM Li Jun-Yan JY Wang Ya-Qin YQ Xu Cheng C Li Ying-Qin YQ He Qing-Mei QM Yang Xiao-Jing XJ Lei Yuan Y Shen Jia-Yi JY Tang Ling-Long LL Chen Lei L Zhou Guan-Qun GQ Li Wen-Fei WF Du Xiao-Jing XJ Guo Rui R Liu Xu X Zhang Yuan Y Zeng Jing J Yun Jing-Ping JP Sun Ying Y Liu Na N Ma Jun J

Molecular cancer 20210111 1

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 no ...[more]

PMID: 33430876

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Project description:PurposeThe current clinical classification of hepatocellular carcinoma (HCC) cannot well predict the patient's possible response to the treatment plan, nor can it predict the patient's prognosis. We use the gene expression patterns of patients with hepatocellular carcinoma to reveal the heterogeneity of hepatocellular carcinoma and analyze the differences in prognosis and immunotherapy response of different immune subtypes.MethodsFirstly, using the hepatocellular carcinoma expression profile data of TCGA, combined with the single sample gene set enrichment analysis (ssGSEA) algorithm, the immune enrichment of the patient's tumor microenvironment was analyzed. Subsequently, the spectral clustering algorithm was used to extract different classifications, and the cohort of hepatocellular carcinoma was divided into 3 subtypes, and the correlation between immune subtypes and clinical characteristics and survival prognosis was established. The patient's risk index is obtained through the prognostic prediction model, suggesting the correlation between the risk index and various types of immune cells.ResultsWe can divide the liver cancer cohort into three subtypes: stromal cell activated immune-enriched type (A-IS), general immune-enriched type (N-IS), and non-immune-enriched type (non-IS). The 3-year survival rate of TCGA's A-IS is higher than that of N-IS and non-IS, and the three components are significantly different (p = 0.017). The 3-year survival rates of ICGC's A-IS and N-IS groups were higher than those of the non-IS group. The analysis of the correlation between the risk index and immune cells showed that the patient's disease risk was significantly positively correlated with cancer-associated fibroblast (CAF) stimulated cell, activated stroma cell, and anti-PD-1 resistant cell.ConclusionThe tumor gene expression characteristics of patients with hepatocellular carcinoma can be used as a basis for clinical patient classification. Different immune subtypes are closely related to survival prognosis. Different immune cell states of patients may lead to different disease risk levels. All these provide important references for the clinical identification and prognosis prediction of hepatocellular carcinoma.

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Dataset Information

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

Publications

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

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