Cargando…
The role of p53 in anti-tumor immunity and response to immunotherapy
p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and D...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434531/ https://www.ncbi.nlm.nih.gov/pubmed/37602328 http://dx.doi.org/10.3389/fmolb.2023.1148389 |
_version_ | 1785091915163631616 |
---|---|
author | Carlsen, Lindsey Zhang, Shengliang Tian, Xiaobing De La Cruz, Arielle George, Andrew Arnoff, Taylor E. El-Deiry, Wafik S. |
author_facet | Carlsen, Lindsey Zhang, Shengliang Tian, Xiaobing De La Cruz, Arielle George, Andrew Arnoff, Taylor E. El-Deiry, Wafik S. |
author_sort | Carlsen, Lindsey |
collection | PubMed |
description | p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and DNA damage repair. p53 also plays an important role in anti-tumor immunity by regulating TRAIL, DR5, TLRs, Fas, PKR, ULBP1/2, and CCL2; T-cell inhibitory ligand PD-L1; pro-inflammatory cytokines; immune cell activation state; and antigen presentation. Genetic alteration of p53 can contribute to immune evasion by influencing immune cell recruitment to the tumor, cytokine secretion in the TME, and inflammatory signaling pathways. In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Indeed, there is clinical evidence to suggest that restoring p53 can induce an anti-cancer immune response in immunologically cold tumors. Clinical trials investigating the combination of p53-restoring compounds or p53-based vaccines with immunotherapy have demonstrated anti-tumor immune activation and tumor regression with heterogeneity across cancer type. In this Review, we discuss the impact of wild-type and mutant p53 on the anti-tumor immune response, outline clinical progress as far as activating p53 to induce an immune response across a variety of cancer types, and highlight open questions limiting effective clinical translation. |
format | Online Article Text |
id | pubmed-10434531 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104345312023-08-18 The role of p53 in anti-tumor immunity and response to immunotherapy Carlsen, Lindsey Zhang, Shengliang Tian, Xiaobing De La Cruz, Arielle George, Andrew Arnoff, Taylor E. El-Deiry, Wafik S. Front Mol Biosci Molecular Biosciences p53 is a transcription factor that regulates the expression of genes involved in tumor suppression. p53 mutations mediate tumorigenesis and occur in approximately 50% of human cancers. p53 regulates hundreds of target genes that induce various cell fates including apoptosis, cell cycle arrest, and DNA damage repair. p53 also plays an important role in anti-tumor immunity by regulating TRAIL, DR5, TLRs, Fas, PKR, ULBP1/2, and CCL2; T-cell inhibitory ligand PD-L1; pro-inflammatory cytokines; immune cell activation state; and antigen presentation. Genetic alteration of p53 can contribute to immune evasion by influencing immune cell recruitment to the tumor, cytokine secretion in the TME, and inflammatory signaling pathways. In some contexts, p53 mutations increase neoantigen load which improves response to immune checkpoint inhibition. Therapeutic restoration of mutated p53 can restore anti-cancer immune cell infiltration and ameliorate pro-tumor signaling to induce tumor regression. Indeed, there is clinical evidence to suggest that restoring p53 can induce an anti-cancer immune response in immunologically cold tumors. Clinical trials investigating the combination of p53-restoring compounds or p53-based vaccines with immunotherapy have demonstrated anti-tumor immune activation and tumor regression with heterogeneity across cancer type. In this Review, we discuss the impact of wild-type and mutant p53 on the anti-tumor immune response, outline clinical progress as far as activating p53 to induce an immune response across a variety of cancer types, and highlight open questions limiting effective clinical translation. Frontiers Media S.A. 2023-08-01 /pmc/articles/PMC10434531/ /pubmed/37602328 http://dx.doi.org/10.3389/fmolb.2023.1148389 Text en Copyright © 2023 Carlsen, Zhang, Tian, De La Cruz, George, Arnoff and El-Deiry. 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 | Molecular Biosciences Carlsen, Lindsey Zhang, Shengliang Tian, Xiaobing De La Cruz, Arielle George, Andrew Arnoff, Taylor E. El-Deiry, Wafik S. The role of p53 in anti-tumor immunity and response to immunotherapy |
title | The role of p53 in anti-tumor immunity and response to immunotherapy |
title_full | The role of p53 in anti-tumor immunity and response to immunotherapy |
title_fullStr | The role of p53 in anti-tumor immunity and response to immunotherapy |
title_full_unstemmed | The role of p53 in anti-tumor immunity and response to immunotherapy |
title_short | The role of p53 in anti-tumor immunity and response to immunotherapy |
title_sort | role of p53 in anti-tumor immunity and response to immunotherapy |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10434531/ https://www.ncbi.nlm.nih.gov/pubmed/37602328 http://dx.doi.org/10.3389/fmolb.2023.1148389 |
work_keys_str_mv | AT carlsenlindsey theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT zhangshengliang theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT tianxiaobing theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT delacruzarielle theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT georgeandrew theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT arnofftaylore theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT eldeirywafiks theroleofp53inantitumorimmunityandresponsetoimmunotherapy AT carlsenlindsey roleofp53inantitumorimmunityandresponsetoimmunotherapy AT zhangshengliang roleofp53inantitumorimmunityandresponsetoimmunotherapy AT tianxiaobing roleofp53inantitumorimmunityandresponsetoimmunotherapy AT delacruzarielle roleofp53inantitumorimmunityandresponsetoimmunotherapy AT georgeandrew roleofp53inantitumorimmunityandresponsetoimmunotherapy AT arnofftaylore roleofp53inantitumorimmunityandresponsetoimmunotherapy AT eldeirywafiks roleofp53inantitumorimmunityandresponsetoimmunotherapy |