Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by...

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Main Authors: Jie Liu, Jiangfan Xu, Tong Zhang, Kailong Xu, Peihua Bao, Zhibo Zhang, Kaiwen Xue, Ruyi He, Lixin Ma, Yang Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2022.791158/full
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author Jie Liu
Jiangfan Xu
Tong Zhang
Kailong Xu
Peihua Bao
Zhibo Zhang
Kaiwen Xue
Ruyi He
Lixin Ma
Yang Wang
author_facet Jie Liu
Jiangfan Xu
Tong Zhang
Kailong Xu
Peihua Bao
Zhibo Zhang
Kaiwen Xue
Ruyi He
Lixin Ma
Yang Wang
author_sort Jie Liu
collection DOAJ
description Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood. A total of 16 different types of cell components of ccRCC were identified. We revealed that there is an overall increase in T-cell and myeloid populations in tumor-infiltrated immune cells compared to normal renal tissue, and the B-cell population in the tumor showed a sharp decrease, which indicates that the cells in tumor tissue undergo strong immune stress. In addition, the cell–cell communication analysis revealed specific or conserved signals in different tissue types, which may aid to uncover the distinct immune response. By combining and analyzing publicly available ccRCC bulk RNA-seq datasets, 10 genes were identified as marker genes in specific cell types, which were significantly associated with poor prognosis. Of note, UBE2C, which may be a good indicator of tumor proliferation, is positively associated with reductions in overall survival and highly associated with tumor grade. Our integrated analysis provides single-cell transcriptomic profiling of ccRCC and their TME, and it unmasked new correlations between gene expression, survival outcomes, and immune cell-type components, enabling us to dissect the dynamic variables in the tumor development process. This resource provides deeper insight into the transcriptome features and immune response of ccRCC and will be helpful in kidney cancer immunotherapy.
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spelling doaj.art-ee73cbb5420c494c9c0f5e54b851271d2022-12-22T00:20:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-06-011310.3389/fimmu.2022.791158791158Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid ImmunotherapyJie Liu0Jiangfan Xu1Tong Zhang2Kailong Xu3Peihua Bao4Zhibo Zhang5Kaiwen Xue6Ruyi He7Lixin Ma8Yang Wang9State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaCollege of Intelligent Systems Science and Engineering, Harbin Engineering University, Harbin, ChinaDepartment of Cardiothoracic Surgery, The 78th Group Army Hospital of Chinese People's Liberation Army, Mudanjiang, ChinaCollege of Chemistry and Chemical Engineering, Hubei University, Wuhan, ChinaSchool of Life Science and Technology, Wuhan Polytechnic University, Wuhan, ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaState Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, ChinaClear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, and it is the major cause of kidney cancer death. Understanding tumor immune microenvironments (TMEs) is critical in cancer immunotherapies. Here, we studied the immune characterization at single-cell resolution by integrating public data of ccRCC across different tissue types, and comparing the transcriptome features and tumor TME differences in tumors, normal adjacent tissue, and peripheral blood. A total of 16 different types of cell components of ccRCC were identified. We revealed that there is an overall increase in T-cell and myeloid populations in tumor-infiltrated immune cells compared to normal renal tissue, and the B-cell population in the tumor showed a sharp decrease, which indicates that the cells in tumor tissue undergo strong immune stress. In addition, the cell–cell communication analysis revealed specific or conserved signals in different tissue types, which may aid to uncover the distinct immune response. By combining and analyzing publicly available ccRCC bulk RNA-seq datasets, 10 genes were identified as marker genes in specific cell types, which were significantly associated with poor prognosis. Of note, UBE2C, which may be a good indicator of tumor proliferation, is positively associated with reductions in overall survival and highly associated with tumor grade. Our integrated analysis provides single-cell transcriptomic profiling of ccRCC and their TME, and it unmasked new correlations between gene expression, survival outcomes, and immune cell-type components, enabling us to dissect the dynamic variables in the tumor development process. This resource provides deeper insight into the transcriptome features and immune response of ccRCC and will be helpful in kidney cancer immunotherapy.https://www.frontiersin.org/articles/10.3389/fimmu.2022.791158/fullsingle celltumor microenvironmentbiomarkerimmunotherapyclear cell renal cell carcinoma
spellingShingle Jie Liu
Jiangfan Xu
Tong Zhang
Kailong Xu
Peihua Bao
Zhibo Zhang
Kaiwen Xue
Ruyi He
Lixin Ma
Yang Wang
Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
Frontiers in Immunology
single cell
tumor microenvironment
biomarker
immunotherapy
clear cell renal cell carcinoma
title Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
title_full Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
title_fullStr Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
title_full_unstemmed Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
title_short Decoding the Immune Microenvironment of Clear Cell Renal Cell Carcinoma by Single-Cell Profiling to Aid Immunotherapy
title_sort decoding the immune microenvironment of clear cell renal cell carcinoma by single cell profiling to aid immunotherapy
topic single cell
tumor microenvironment
biomarker
immunotherapy
clear cell renal cell carcinoma
url https://www.frontiersin.org/articles/10.3389/fimmu.2022.791158/full
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