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Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3

The success of CD8(+) T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer...

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Autores principales: Boulpicante, Mathilde, Darrigrand, Romain, Pierson, Alison, Salgues, Valérie, Rouillon, Marine, Gaudineau, Benoit, Khaled, Mehdi, Cattaneo, Angela, Bachi, Angela, Cascio, Paolo, Apcher, Sébastien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458623/
https://www.ncbi.nlm.nih.gov/pubmed/32923122
http://dx.doi.org/10.1080/2162402X.2020.1761205
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author Boulpicante, Mathilde
Darrigrand, Romain
Pierson, Alison
Salgues, Valérie
Rouillon, Marine
Gaudineau, Benoit
Khaled, Mehdi
Cattaneo, Angela
Bachi, Angela
Cascio, Paolo
Apcher, Sébastien
author_facet Boulpicante, Mathilde
Darrigrand, Romain
Pierson, Alison
Salgues, Valérie
Rouillon, Marine
Gaudineau, Benoit
Khaled, Mehdi
Cattaneo, Angela
Bachi, Angela
Cascio, Paolo
Apcher, Sébastien
author_sort Boulpicante, Mathilde
collection PubMed
description The success of CD8(+) T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance. These findings unveil a previously unexpected role for PSME3 in antigen processing and identify PSME3 as a druggable target to improve the efficacy of cancer immunotherapy.
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spelling pubmed-74586232020-09-11 Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3 Boulpicante, Mathilde Darrigrand, Romain Pierson, Alison Salgues, Valérie Rouillon, Marine Gaudineau, Benoit Khaled, Mehdi Cattaneo, Angela Bachi, Angela Cascio, Paolo Apcher, Sébastien Oncoimmunology Original Research The success of CD8(+) T cell-based cancer immunotherapy emphasizes the importance of understanding the mechanisms of generation of MHC-I peptide ligands and the possible pathways of tumor cell escape from immunosurveillance. Recently, we showed that peptides generated in the nucleus during a pioneer round of mRNA translation (pioneer translation products, or PTPs) are an important source of tumor specific peptides which correlates with the aberrant splicing and transcription events associated with oncogenesis. Here we show that up-regulation of PSME3 proteasome activator in cancer cells results in increased destruction of PTP-derived peptides in the nucleus thus enabling cancer cell to subvert immunosurveillance. These findings unveil a previously unexpected role for PSME3 in antigen processing and identify PSME3 as a druggable target to improve the efficacy of cancer immunotherapy. Taylor & Francis 2020-05-21 /pmc/articles/PMC7458623/ /pubmed/32923122 http://dx.doi.org/10.1080/2162402X.2020.1761205 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Boulpicante, Mathilde
Darrigrand, Romain
Pierson, Alison
Salgues, Valérie
Rouillon, Marine
Gaudineau, Benoit
Khaled, Mehdi
Cattaneo, Angela
Bachi, Angela
Cascio, Paolo
Apcher, Sébastien
Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title_full Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title_fullStr Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title_full_unstemmed Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title_short Tumors escape immunosurveillance by overexpressing the proteasome activator PSME3
title_sort tumors escape immunosurveillance by overexpressing the proteasome activator psme3
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458623/
https://www.ncbi.nlm.nih.gov/pubmed/32923122
http://dx.doi.org/10.1080/2162402X.2020.1761205
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