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Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases

The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and devel...

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Autores principales: Sim, Wynne, Lim, Wei-Meng, Hii, Ling-Wei, Leong, Chee-Onn, Mai, Chun-Wai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150054/
https://www.ncbi.nlm.nih.gov/pubmed/35664961
http://dx.doi.org/10.3748/wjg.v28.i18.1934
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author Sim, Wynne
Lim, Wei-Meng
Hii, Ling-Wei
Leong, Chee-Onn
Mai, Chun-Wai
author_facet Sim, Wynne
Lim, Wei-Meng
Hii, Ling-Wei
Leong, Chee-Onn
Mai, Chun-Wai
author_sort Sim, Wynne
collection PubMed
description The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and development. Immune evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic cancer. Compared with other cancers, pancreatic cancer has a tumor microenvironment that can resist most treatment modalities, including emerging immunotherapy. Sadly, the use of immunotherapy has yet to bring significant clinical breakthrough among pancreatic cancer patients, suggesting that pancreatic cancer has successfully evaded immunomodulation. In this review, we summarize the impact of genetic alteration and epigenetic modification (especially histone deacetylases, HDAC) on immune evasion in pancreatic cancer. HDAC overexpression significantly suppresses tumor suppressor genes, contributing to tumor growth and progression. We review the evidence on HDAC inhibitors in tumor eradication, improving T cells activation, restoring tumor immunogenicity, and modulating programmed death 1 interaction. We provide our perspective in targeting HDAC as a strategy to reverse immune evasion in pancreatic cancer.
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spelling pubmed-91500542022-06-04 Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases Sim, Wynne Lim, Wei-Meng Hii, Ling-Wei Leong, Chee-Onn Mai, Chun-Wai World J Gastroenterol Minireviews The immune system plays a vital role in maintaining the delicate balance between immune recognition and tumor development. Regardless, it is not uncommon that cancerous cells can intelligently acquire abilities to bypass the antitumor immune responses, thus allowing continuous tumor growth and development. Immune evasion has emerged as a significant factor contributing to the progression and immune resistance of pancreatic cancer. Compared with other cancers, pancreatic cancer has a tumor microenvironment that can resist most treatment modalities, including emerging immunotherapy. Sadly, the use of immunotherapy has yet to bring significant clinical breakthrough among pancreatic cancer patients, suggesting that pancreatic cancer has successfully evaded immunomodulation. In this review, we summarize the impact of genetic alteration and epigenetic modification (especially histone deacetylases, HDAC) on immune evasion in pancreatic cancer. HDAC overexpression significantly suppresses tumor suppressor genes, contributing to tumor growth and progression. We review the evidence on HDAC inhibitors in tumor eradication, improving T cells activation, restoring tumor immunogenicity, and modulating programmed death 1 interaction. We provide our perspective in targeting HDAC as a strategy to reverse immune evasion in pancreatic cancer. Baishideng Publishing Group Inc 2022-05-14 2022-05-14 /pmc/articles/PMC9150054/ /pubmed/35664961 http://dx.doi.org/10.3748/wjg.v28.i18.1934 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Minireviews
Sim, Wynne
Lim, Wei-Meng
Hii, Ling-Wei
Leong, Chee-Onn
Mai, Chun-Wai
Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title_full Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title_fullStr Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title_full_unstemmed Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title_short Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
title_sort targeting pancreatic cancer immune evasion by inhibiting histone deacetylases
topic Minireviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150054/
https://www.ncbi.nlm.nih.gov/pubmed/35664961
http://dx.doi.org/10.3748/wjg.v28.i18.1934
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