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

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-enri...

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Autores principales: Chen, Yu-Pei, Lv, Jia-Wei, Mao, Yan-Ping, Li, Xiao-Min, Li, Jun-Yan, Wang, Ya-Qin, Xu, Cheng, Li, Ying-Qin, He, Qing-Mei, Yang, Xiao-Jing, Lei, Yuan, Shen, Jia-Yi, Tang, Ling-Long, Chen, Lei, Zhou, Guan-Qun, Li, Wen-Fei, Du, Xiao-Jing, Guo, Rui, Liu, Xu, Zhang, Yuan, Zeng, Jing, Yun, Jing-Ping, Sun, Ying, Liu, Na, Ma, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798236/
https://www.ncbi.nlm.nih.gov/pubmed/33430876
http://dx.doi.org/10.1186/s12943-020-01292-5
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author Chen, Yu-Pei
Lv, Jia-Wei
Mao, Yan-Ping
Li, Xiao-Min
Li, Jun-Yan
Wang, Ya-Qin
Xu, Cheng
Li, Ying-Qin
He, Qing-Mei
Yang, Xiao-Jing
Lei, Yuan
Shen, Jia-Yi
Tang, Ling-Long
Chen, Lei
Zhou, Guan-Qun
Li, Wen-Fei
Du, Xiao-Jing
Guo, Rui
Liu, Xu
Zhang, Yuan
Zeng, Jing
Yun, Jing-Ping
Sun, Ying
Liu, Na
Ma, Jun
author_facet Chen, Yu-Pei
Lv, Jia-Wei
Mao, Yan-Ping
Li, Xiao-Min
Li, Jun-Yan
Wang, Ya-Qin
Xu, Cheng
Li, Ying-Qin
He, Qing-Mei
Yang, Xiao-Jing
Lei, Yuan
Shen, Jia-Yi
Tang, Ling-Long
Chen, Lei
Zhou, Guan-Qun
Li, Wen-Fei
Du, Xiao-Jing
Guo, Rui
Liu, Xu
Zhang, Yuan
Zeng, Jing
Yun, Jing-Ping
Sun, Ying
Liu, Na
Ma, Jun
author_sort Chen, Yu-Pei
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-020-01292-5.
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spelling pubmed-77982362021-01-11 Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses Chen, Yu-Pei Lv, Jia-Wei Mao, Yan-Ping Li, Xiao-Min Li, Jun-Yan Wang, Ya-Qin Xu, Cheng Li, Ying-Qin He, Qing-Mei Yang, Xiao-Jing Lei, Yuan Shen, Jia-Yi Tang, Ling-Long Chen, Lei Zhou, Guan-Qun Li, Wen-Fei Du, Xiao-Jing Guo, Rui Liu, Xu Zhang, Yuan Zeng, Jing Yun, Jing-Ping Sun, Ying Liu, Na Ma, Jun Mol Cancer Letter 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12943-020-01292-5. BioMed Central 2021-01-11 /pmc/articles/PMC7798236/ /pubmed/33430876 http://dx.doi.org/10.1186/s12943-020-01292-5 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Letter
Chen, Yu-Pei
Lv, Jia-Wei
Mao, Yan-Ping
Li, Xiao-Min
Li, Jun-Yan
Wang, Ya-Qin
Xu, Cheng
Li, Ying-Qin
He, Qing-Mei
Yang, Xiao-Jing
Lei, Yuan
Shen, Jia-Yi
Tang, Ling-Long
Chen, Lei
Zhou, Guan-Qun
Li, Wen-Fei
Du, Xiao-Jing
Guo, Rui
Liu, Xu
Zhang, Yuan
Zeng, Jing
Yun, Jing-Ping
Sun, Ying
Liu, Na
Ma, Jun
Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title_full Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title_fullStr Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title_full_unstemmed Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title_short Unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
title_sort unraveling tumour microenvironment heterogeneity in nasopharyngeal carcinoma identifies biologically distinct immune subtypes predicting prognosis and immunotherapy responses
topic Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798236/
https://www.ncbi.nlm.nih.gov/pubmed/33430876
http://dx.doi.org/10.1186/s12943-020-01292-5
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