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High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer

Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequen...

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Autores principales: Ke, Shouyu, Xie, Feng, Guo, Yixian, Chen, Jieqiong, Wang, Zeyu, Yu, Yimeng, Geng, Haigang, Xu, Danhua, Liu, Xu, Xia, Xiang, Yu, Fengrong, Zhu, Chunchao, Zhang, Zizhen, Zhao, Gang, Li, Bin, Zhao, Wenyi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676631/
https://www.ncbi.nlm.nih.gov/pubmed/36419848
http://dx.doi.org/10.1016/j.isci.2022.105529
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author Ke, Shouyu
Xie, Feng
Guo, Yixian
Chen, Jieqiong
Wang, Zeyu
Yu, Yimeng
Geng, Haigang
Xu, Danhua
Liu, Xu
Xia, Xiang
Yu, Fengrong
Zhu, Chunchao
Zhang, Zizhen
Zhao, Gang
Li, Bin
Zhao, Wenyi
author_facet Ke, Shouyu
Xie, Feng
Guo, Yixian
Chen, Jieqiong
Wang, Zeyu
Yu, Yimeng
Geng, Haigang
Xu, Danhua
Liu, Xu
Xia, Xiang
Yu, Fengrong
Zhu, Chunchao
Zhang, Zizhen
Zhao, Gang
Li, Bin
Zhao, Wenyi
author_sort Ke, Shouyu
collection PubMed
description Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied.
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spelling pubmed-96766312022-11-22 High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer Ke, Shouyu Xie, Feng Guo, Yixian Chen, Jieqiong Wang, Zeyu Yu, Yimeng Geng, Haigang Xu, Danhua Liu, Xu Xia, Xiang Yu, Fengrong Zhu, Chunchao Zhang, Zizhen Zhao, Gang Li, Bin Zhao, Wenyi iScience Article Immunotherapy targeting glucocorticoid-induced TNFR-related protein (GITR) exhibited strong anti-tumor capacity in mouse model but poor efficacy in clinical trials. This may be attributed to the different GITR expression mode between human and mouse. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of human gastric cancer (GC) and used flow to explore the GITR expression across T cell subsets and tissue types in GC patients. We revealed that GITR+ CD4 T cells, including regulatory CD4 T (Treg) cells and conventional CD4 T (Tconv) cells, might contribute to the immunosuppressive microenvironment in GC. The enrichment of these cells was associated with a worse prognosis. Moreover, we found the cellular distribution of GITR protein in Treg cells was microenvironment dependent. In conclusion, GITR is still an important immune checkpoint need to be studied. Elsevier 2022-11-07 /pmc/articles/PMC9676631/ /pubmed/36419848 http://dx.doi.org/10.1016/j.isci.2022.105529 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Ke, Shouyu
Xie, Feng
Guo, Yixian
Chen, Jieqiong
Wang, Zeyu
Yu, Yimeng
Geng, Haigang
Xu, Danhua
Liu, Xu
Xia, Xiang
Yu, Fengrong
Zhu, Chunchao
Zhang, Zizhen
Zhao, Gang
Li, Bin
Zhao, Wenyi
High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title_full High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title_fullStr High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title_full_unstemmed High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title_short High-level of intratumoral GITR+ CD4 T cells associate with poor prognosis in gastric cancer
title_sort high-level of intratumoral gitr+ cd4 t cells associate with poor prognosis in gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676631/
https://www.ncbi.nlm.nih.gov/pubmed/36419848
http://dx.doi.org/10.1016/j.isci.2022.105529
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