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Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment

The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence sugges...

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Detalles Bibliográficos
Autores principales: Cui, Yan, Guo, Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133937/
https://www.ncbi.nlm.nih.gov/pubmed/27869779
http://dx.doi.org/10.3390/ijms17111942
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author Cui, Yan
Guo, Gang
author_facet Cui, Yan
Guo, Gang
author_sort Cui, Yan
collection PubMed
description The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome.
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spelling pubmed-51339372016-12-12 Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment Cui, Yan Guo, Gang Int J Mol Sci Review The tumor suppressor p53 is the most frequently mutated gene in human cancers. Most of the mutations are missense leading to loss of p53 function in inducing apoptosis and senescence. In addition to these autonomous effects of p53 inactivation/dysfunction on tumorigenesis, compelling evidence suggests that p53 mutation/inactivation also leads to gain-of-function or activation of non-autonomous pathways, which either directly or indirectly promote tumorigenesis. Experimental and clinical results suggest that p53 dysfunction fuels pro-tumor inflammation and serves as an immunological gain-of-function driver of tumorigenesis via skewing immune landscape of the tumor microenvironment (TME). It is now increasingly appreciated that p53 dysfunction in various cellular compartments of the TME leads to immunosuppression and immune evasion. Although our understanding of the cellular and molecular processes that link p53 activity to host immune regulation is still incomplete, it is clear that activating/reactivating the p53 pathway in the TME also represents a compelling immunological strategy to reverse immunosuppression and enhance antitumor immunity. Here, we review our current understanding of the potential cellular and molecular mechanisms by which p53 participates in immune regulation and discuss how targeting the p53 pathway can be exploited to alter the immunological landscape of tumors for maximizing therapeutic outcome. MDPI 2016-11-19 /pmc/articles/PMC5133937/ /pubmed/27869779 http://dx.doi.org/10.3390/ijms17111942 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Cui, Yan
Guo, Gang
Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title_full Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title_fullStr Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title_full_unstemmed Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title_short Immunomodulatory Function of the Tumor Suppressor p53 in Host Immune Response and the Tumor Microenvironment
title_sort immunomodulatory function of the tumor suppressor p53 in host immune response and the tumor microenvironment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133937/
https://www.ncbi.nlm.nih.gov/pubmed/27869779
http://dx.doi.org/10.3390/ijms17111942
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