The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response

Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a subs...

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Autores principales:	Audrey Moatti, José L. Cohen
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	regulatory T cells (Tregs) immunotherapies cancer immunosuppression anti-tumor action Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/f8f222ca52204035ade5b7abc1e9360d
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spelling	oai:doaj.org-article:f8f222ca52204035ade5b7abc1e9360d2021-11-05T23:37:50ZThe TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response2296-634X10.3389/fcell.2021.725473https://doaj.org/article/f8f222ca52204035ade5b7abc1e9360d2021-10-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.725473/fullhttps://doaj.org/toc/2296-634XNewly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackle this immune brake by targeting the suppressive action of Tregs on the anti-tumoral response. It was recently demonstrated that the tumor necrosis factor alpha (TNF-α) tumor necrosis factor receptor 2 (TNFR2) is critical for the phenotypic stabilization and suppressive function of human and mouse Tregs. The broad non-specific effects of TNF-α infusion in patients initially led clinicians to abandon this signaling pathway as first-line therapy against neoplasms. Previously unrecognized, TNFR2 has emerged recently as a legitimate target for anti-cancer immune checkpoint therapy. Considering the accumulation of pre-clinical data on the role of TNFR2 and clinical reports of TNFR2+ Tregs and tumor cells in cancer patients, it is now clear that a TNFR2-centered approach could be a viable strategy, once again making the TNF-α pathway a promising anti-cancer target. Here, we review the role of the TNFR2 signaling pathway in tolerance and the equilibrium of T cell responses and its connections with oncogenesis. We analyze recent discoveries concerning the targeting of TNFR2 in cancer, as well as the advantages, limitations, and perspectives of such a strategy.Audrey MoattiAudrey MoattiJosé L. CohenJosé L. CohenFrontiers Media S.A.articleregulatory T cells (Tregs)immunotherapiescancerimmunosuppressionanti-tumor actionBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	regulatory T cells (Tregs) immunotherapies cancer immunosuppression anti-tumor action Biology (General) QH301-705.5
spellingShingle	regulatory T cells (Tregs) immunotherapies cancer immunosuppression anti-tumor action Biology (General) QH301-705.5 Audrey Moatti Audrey Moatti José L. Cohen José L. Cohen The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
description	Newly discovered anti-cancer immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cells, focus on spurring the anti-tumor effector T cell (Teff) response. Although such strategies have already demonstrated a sustained beneficial effect in certain malignancies, a substantial proportion of treated patients does not respond. CD4+FOXP3+ regulatory T cells (Tregs), a suppressive subset of T cells, can impair anti-tumor responses and reduce the efficacy of currently available immunotherapies. An alternative view that has emerged over the last decade proposes to tackle this immune brake by targeting the suppressive action of Tregs on the anti-tumoral response. It was recently demonstrated that the tumor necrosis factor alpha (TNF-α) tumor necrosis factor receptor 2 (TNFR2) is critical for the phenotypic stabilization and suppressive function of human and mouse Tregs. The broad non-specific effects of TNF-α infusion in patients initially led clinicians to abandon this signaling pathway as first-line therapy against neoplasms. Previously unrecognized, TNFR2 has emerged recently as a legitimate target for anti-cancer immune checkpoint therapy. Considering the accumulation of pre-clinical data on the role of TNFR2 and clinical reports of TNFR2+ Tregs and tumor cells in cancer patients, it is now clear that a TNFR2-centered approach could be a viable strategy, once again making the TNF-α pathway a promising anti-cancer target. Here, we review the role of the TNFR2 signaling pathway in tolerance and the equilibrium of T cell responses and its connections with oncogenesis. We analyze recent discoveries concerning the targeting of TNFR2 in cancer, as well as the advantages, limitations, and perspectives of such a strategy.
format	article
author	Audrey Moatti Audrey Moatti José L. Cohen José L. Cohen
author_facet	Audrey Moatti Audrey Moatti José L. Cohen José L. Cohen
author_sort	Audrey Moatti
title	The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
title_short	The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
title_full	The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
title_fullStr	The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
title_full_unstemmed	The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response
title_sort	tnf-α/tnfr2 pathway: targeting a brake to release the anti-tumor immune response
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f8f222ca52204035ade5b7abc1e9360d
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The TNF-α/TNFR2 Pathway: Targeting a Brake to Release the Anti-tumor Immune Response

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