mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion

We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4+ and CD8+ cells...

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Autores principales:	Benedetta De Ponte Conti, Annarita Miluzio, Fabio Grassi, Sergio Abrignani, Stefano Biffo, Sara Ricciardi
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	CD4+ CD8+ Treg translation Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fab3f83dd8e643acb9b5dca1084763fe
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spelling	oai:doaj.org-article:fab3f83dd8e643acb9b5dca1084763fe2021-11-17T12:51:39ZmTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion10.7554/eLife.690152050-084Xe69015https://doaj.org/article/fab3f83dd8e643acb9b5dca1084763fe2021-11-01T00:00:00Zhttps://elifesciences.org/articles/69015https://doaj.org/toc/2050-084XWe performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4+ and CD8+ cells in tumors, compared to normal tissues. High translation levels are associated with phospho-S6 labeling downstream of mTORC1 activation, whereas low levels correlate with hypoxic areas, in agreement with data showing that T cell receptor stimulation and hypoxia act as translation stimulators and inhibitors, respectively. Additional analyses revealed the specific phenotype of translating TILs. CD8+ translating cells have enriched expression of IFN-γ and CD-39, and reduced SLAMF6, pointing to a cytotoxic phenotype. CD4+ translating cells are mostly regulatory T cells (Tregs) with enriched levels of CTLA-4 and Ki67, suggesting an expanding immunosuppressive phenotype. In conclusion, the majority of translationally active TILs is represented by cytotoxic CD8+ and suppressive CD4+ Tregs, implying that other subsets may be largely composed by inactive bystanders.Benedetta De Ponte ContiAnnarita MiluzioFabio GrassiSergio AbrignaniStefano BiffoSara RicciardieLife Sciences Publications LtdarticleCD4+CD8+TregtranslationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD4+ CD8+ Treg translation Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	CD4+ CD8+ Treg translation Medicine R Science Q Biology (General) QH301-705.5 Benedetta De Ponte Conti Annarita Miluzio Fabio Grassi Sergio Abrignani Stefano Biffo Sara Ricciardi mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
description	We performed a systematic analysis of the translation rate of tumor-infiltrating lymphocytes (TILs) and the microenvironment inputs affecting it, both in humans and in mice. Measurement of puromycin incorporation, a proxy of protein synthesis, revealed an increase of translating CD4+ and CD8+ cells in tumors, compared to normal tissues. High translation levels are associated with phospho-S6 labeling downstream of mTORC1 activation, whereas low levels correlate with hypoxic areas, in agreement with data showing that T cell receptor stimulation and hypoxia act as translation stimulators and inhibitors, respectively. Additional analyses revealed the specific phenotype of translating TILs. CD8+ translating cells have enriched expression of IFN-γ and CD-39, and reduced SLAMF6, pointing to a cytotoxic phenotype. CD4+ translating cells are mostly regulatory T cells (Tregs) with enriched levels of CTLA-4 and Ki67, suggesting an expanding immunosuppressive phenotype. In conclusion, the majority of translationally active TILs is represented by cytotoxic CD8+ and suppressive CD4+ Tregs, implying that other subsets may be largely composed by inactive bystanders.
format	article
author	Benedetta De Ponte Conti Annarita Miluzio Fabio Grassi Sergio Abrignani Stefano Biffo Sara Ricciardi
author_facet	Benedetta De Ponte Conti Annarita Miluzio Fabio Grassi Sergio Abrignani Stefano Biffo Sara Ricciardi
author_sort	Benedetta De Ponte Conti
title	mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
title_short	mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
title_full	mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
title_fullStr	mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
title_full_unstemmed	mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion
title_sort	mtor-dependent translation drives tumor infiltrating cd8+ effector and cd4+ treg cells expansion
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/fab3f83dd8e643acb9b5dca1084763fe
work_keys_str_mv	AT benedettadeponteconti mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion AT annaritamiluzio mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion AT fabiograssi mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion AT sergioabrignani mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion AT stefanobiffo mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion AT sararicciardi mtordependenttranslationdrivestumorinfiltratingcd8effectorandcd4tregcellsexpansion
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mTOR-dependent translation drives tumor infiltrating CD8+ effector and CD4+ Treg cells expansion

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