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BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer

BRAF mutated colon cancer presents with poor survival, and the treatment strategies are controversial. The tumor microenvironment, which plays a key role in tumorigenesis as well as responses to treatments, of this subtype is largely unknown. In the present study, we analyzed the differences of immu...

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Autores principales: Cen, Shuyi, Liu, Kun, Zheng, Yu, Shan, Jianzhen, Jing, Chao, Gao, Jiale, Pan, Hongming, Bai, Zhigang, Liu, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350390/
https://www.ncbi.nlm.nih.gov/pubmed/34381786
http://dx.doi.org/10.3389/fcell.2021.705060
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author Cen, Shuyi
Liu, Kun
Zheng, Yu
Shan, Jianzhen
Jing, Chao
Gao, Jiale
Pan, Hongming
Bai, Zhigang
Liu, Zhen
author_facet Cen, Shuyi
Liu, Kun
Zheng, Yu
Shan, Jianzhen
Jing, Chao
Gao, Jiale
Pan, Hongming
Bai, Zhigang
Liu, Zhen
author_sort Cen, Shuyi
collection PubMed
description BRAF mutated colon cancer presents with poor survival, and the treatment strategies are controversial. The tumor microenvironment, which plays a key role in tumorigenesis as well as responses to treatments, of this subtype is largely unknown. In the present study, we analyzed the differences of immune microenvironments between BRAF mutated and BRAF wild-type colon cancer utilizing datasets from The Cancer Genome Atlas and Gene Expression Omnibus and confirmed the findings by tissue specimens of patients. We found that BRAF mutated colon cancer had more stromal cells, more immune cell infiltration, and lower tumor purity. Many immunotherapeutic targets, including PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3, were highly expressed in BRAF mutated patients. BRAF mutation was also correlated with higher proportions of neutrophils and macrophages M1, and lower proportions of plasma cells, dendritic cells resting, and T cells CD4 naïve. In conclusion, our study demonstrates a different pattern of the immune microenvironment in BRAF mutated colon cancer and provides insights into the future use of checkpoint inhibitors in this subgroup of patients.
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spelling pubmed-83503902021-08-10 BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer Cen, Shuyi Liu, Kun Zheng, Yu Shan, Jianzhen Jing, Chao Gao, Jiale Pan, Hongming Bai, Zhigang Liu, Zhen Front Cell Dev Biol Cell and Developmental Biology BRAF mutated colon cancer presents with poor survival, and the treatment strategies are controversial. The tumor microenvironment, which plays a key role in tumorigenesis as well as responses to treatments, of this subtype is largely unknown. In the present study, we analyzed the differences of immune microenvironments between BRAF mutated and BRAF wild-type colon cancer utilizing datasets from The Cancer Genome Atlas and Gene Expression Omnibus and confirmed the findings by tissue specimens of patients. We found that BRAF mutated colon cancer had more stromal cells, more immune cell infiltration, and lower tumor purity. Many immunotherapeutic targets, including PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3, were highly expressed in BRAF mutated patients. BRAF mutation was also correlated with higher proportions of neutrophils and macrophages M1, and lower proportions of plasma cells, dendritic cells resting, and T cells CD4 naïve. In conclusion, our study demonstrates a different pattern of the immune microenvironment in BRAF mutated colon cancer and provides insights into the future use of checkpoint inhibitors in this subgroup of patients. Frontiers Media S.A. 2021-07-26 /pmc/articles/PMC8350390/ /pubmed/34381786 http://dx.doi.org/10.3389/fcell.2021.705060 Text en Copyright © 2021 Cen, Liu, Zheng, Shan, Jing, Gao, Pan, Bai and Liu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Cen, Shuyi
Liu, Kun
Zheng, Yu
Shan, Jianzhen
Jing, Chao
Gao, Jiale
Pan, Hongming
Bai, Zhigang
Liu, Zhen
BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title_full BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title_fullStr BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title_full_unstemmed BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title_short BRAF Mutation as a Potential Therapeutic Target for Checkpoint Inhibitors: A Comprehensive Analysis of Immune Microenvironment in BRAF Mutated Colon Cancer
title_sort braf mutation as a potential therapeutic target for checkpoint inhibitors: a comprehensive analysis of immune microenvironment in braf mutated colon cancer
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350390/
https://www.ncbi.nlm.nih.gov/pubmed/34381786
http://dx.doi.org/10.3389/fcell.2021.705060
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