Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer

The tumor microenvironment (TME) is mainly composed of tumor cells, tumor-infiltrating immune cells, and stromal components. It plays an essential role in the prognosis and therapeutic response of patients. Nonetheless, the TME landscape of urothelial cancer (UC) has not been fully elucidated. In th...

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Autores principales:	Guangdi Chu, Wenhong Shan, Xiaoyu Ji, Yonghua Wang, Haitao Niu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	tumor microenvironment immunotherapy urothelial cancer macrophage immune checkpoint Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/09939647abcc4b209188ff5170a81aef
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spelling	oai:doaj.org-article:09939647abcc4b209188ff5170a81aef2021-12-03T06:53:58ZMulti-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer2296-634X10.3389/fcell.2021.764125https://doaj.org/article/09939647abcc4b209188ff5170a81aef2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.764125/fullhttps://doaj.org/toc/2296-634XThe tumor microenvironment (TME) is mainly composed of tumor cells, tumor-infiltrating immune cells, and stromal components. It plays an essential role in the prognosis and therapeutic response of patients. Nonetheless, the TME landscape of urothelial cancer (UC) has not been fully elucidated. In this study, we systematically analyzed several UC cohorts, and three types of TME patterns (stromal-activation subtype, immune-enriched subtype and immune-suppressive subtype) were defined. The tumor microenvironment signature (TMSig) was constructed by modified Lasso penalized regression. Patients were stratified into high- and low-TMSig score groups. The low-score group had a better prognosis (p < 0.0001), higher M1 macrophage infiltration (p < 0.01), better response to immunotherapy (p < 0.05), and more similar molecular characteristics to the luminal (differentiated) subtype. The accuracy of the TMSig for predicting the immunotherapy response was also verified in three independent cohorts. We highlighted that the TMSig is an effective predictor of patient prognosis and immunotherapy response. Quantitative evaluation of a single sample is valuable for us to combine histopathological and molecular characteristics to comprehensively evaluate the status of the patient. Targeted macrophage treatment has great potential for the individualized precision therapy of UC patients.Guangdi ChuWenhong ShanXiaoyu JiYonghua WangHaitao NiuFrontiers Media S.A.articletumor microenvironmentimmunotherapyurothelial cancermacrophageimmune checkpointBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tumor microenvironment immunotherapy urothelial cancer macrophage immune checkpoint Biology (General) QH301-705.5
spellingShingle	tumor microenvironment immunotherapy urothelial cancer macrophage immune checkpoint Biology (General) QH301-705.5 Guangdi Chu Wenhong Shan Xiaoyu Ji Yonghua Wang Haitao Niu Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
description	The tumor microenvironment (TME) is mainly composed of tumor cells, tumor-infiltrating immune cells, and stromal components. It plays an essential role in the prognosis and therapeutic response of patients. Nonetheless, the TME landscape of urothelial cancer (UC) has not been fully elucidated. In this study, we systematically analyzed several UC cohorts, and three types of TME patterns (stromal-activation subtype, immune-enriched subtype and immune-suppressive subtype) were defined. The tumor microenvironment signature (TMSig) was constructed by modified Lasso penalized regression. Patients were stratified into high- and low-TMSig score groups. The low-score group had a better prognosis (p < 0.0001), higher M1 macrophage infiltration (p < 0.01), better response to immunotherapy (p < 0.05), and more similar molecular characteristics to the luminal (differentiated) subtype. The accuracy of the TMSig for predicting the immunotherapy response was also verified in three independent cohorts. We highlighted that the TMSig is an effective predictor of patient prognosis and immunotherapy response. Quantitative evaluation of a single sample is valuable for us to combine histopathological and molecular characteristics to comprehensively evaluate the status of the patient. Targeted macrophage treatment has great potential for the individualized precision therapy of UC patients.
format	article
author	Guangdi Chu Wenhong Shan Xiaoyu Ji Yonghua Wang Haitao Niu
author_facet	Guangdi Chu Wenhong Shan Xiaoyu Ji Yonghua Wang Haitao Niu
author_sort	Guangdi Chu
title	Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
title_short	Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
title_full	Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
title_fullStr	Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
title_full_unstemmed	Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer
title_sort	multi-omics analysis of novel signature for immunotherapy response and tumor microenvironment regulation patterns in urothelial cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/09939647abcc4b209188ff5170a81aef
work_keys_str_mv	AT guangdichu multiomicsanalysisofnovelsignatureforimmunotherapyresponseandtumormicroenvironmentregulationpatternsinurothelialcancer AT wenhongshan multiomicsanalysisofnovelsignatureforimmunotherapyresponseandtumormicroenvironmentregulationpatternsinurothelialcancer AT xiaoyuji multiomicsanalysisofnovelsignatureforimmunotherapyresponseandtumormicroenvironmentregulationpatternsinurothelialcancer AT yonghuawang multiomicsanalysisofnovelsignatureforimmunotherapyresponseandtumormicroenvironmentregulationpatternsinurothelialcancer AT haitaoniu multiomicsanalysisofnovelsignatureforimmunotherapyresponseandtumormicroenvironmentregulationpatternsinurothelialcancer
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Multi-Omics Analysis of Novel Signature for Immunotherapy Response and Tumor Microenvironment Regulation Patterns in Urothelial Cancer

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