Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment

In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, e...

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Autores principales:	Glauco Akelinghton Freire Vitiello, Wallax Augusto Silva Ferreira, Vladmir Cláudio Cordeiro de Lima, Tiago da Silva Medina
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	antiviral immune response antitumor immunity oncolytic viruses interferons epigenetic regulation endogenous retroviral elements Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/3427a3d049fa4ac3a23b500560336100
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spelling	oai:doaj.org-article:3427a3d049fa4ac3a23b5005603361002021-12-02T06:40:59ZAntiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment1664-322410.3389/fimmu.2021.782852https://doaj.org/article/3427a3d049fa4ac3a23b5005603361002021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.782852/fullhttps://doaj.org/toc/1664-3224In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, epigenetic regulation of EREs is crucial to maintain steady-state conditions and cell homeostasis. In line with this, epigenetic disruptions within steady-state cells can lead to cancer development and trigger the release of EREs into the cytoplasmic compartment. As such, detection of viral molecules by intracellular innate immune sensors leads to the production of type I and type III interferons that act to induce an antiviral state, thus restraining viral replication. This knowledge has recently gained momentum due to the possibility of triggering intratumoral activation of interferon responses, which could be used as an adjuvant to elicit strong anti-tumor immune responses that ultimately lead to a cascade of cytokine production. Accordingly, several therapeutic approaches are currently being tested using this rationale to improve responses to cancer immunotherapies. In this review, we discuss the immune mechanisms operating in viral infections, show evidence that exogenous viruses and endogenous retroviruses in cancer may enhance tumor immunogenicity, dissect the epigenetic control of EREs, and point to interferon pathway activation in the tumor milieu as a promising molecular predictive marker and immunotherapy target. Finally, we briefly discuss current strategies to modulate these responses within tumor tissues, including the clinical use of innate immune receptor agonists and DNA demethylating agents.Glauco Akelinghton Freire VitielloWallax Augusto Silva FerreiraWallax Augusto Silva FerreiraVladmir Cláudio Cordeiro de LimaTiago da Silva MedinaTiago da Silva MedinaFrontiers Media S.A.articleantiviral immune responseantitumor immunityoncolytic virusesinterferonsepigenetic regulationendogenous retroviral elementsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antiviral immune response antitumor immunity oncolytic viruses interferons epigenetic regulation endogenous retroviral elements Immunologic diseases. Allergy RC581-607
spellingShingle	antiviral immune response antitumor immunity oncolytic viruses interferons epigenetic regulation endogenous retroviral elements Immunologic diseases. Allergy RC581-607 Glauco Akelinghton Freire Vitiello Wallax Augusto Silva Ferreira Wallax Augusto Silva Ferreira Vladmir Cláudio Cordeiro de Lima Tiago da Silva Medina Tiago da Silva Medina Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
description	In recent years, it became apparent that cancers either associated with viral infections or aberrantly expressing endogenous retroviral elements (EREs) are more immunogenic, exhibiting an intense intra-tumor immune cell infiltration characterized by a robust cytolytic apparatus. On the other hand, epigenetic regulation of EREs is crucial to maintain steady-state conditions and cell homeostasis. In line with this, epigenetic disruptions within steady-state cells can lead to cancer development and trigger the release of EREs into the cytoplasmic compartment. As such, detection of viral molecules by intracellular innate immune sensors leads to the production of type I and type III interferons that act to induce an antiviral state, thus restraining viral replication. This knowledge has recently gained momentum due to the possibility of triggering intratumoral activation of interferon responses, which could be used as an adjuvant to elicit strong anti-tumor immune responses that ultimately lead to a cascade of cytokine production. Accordingly, several therapeutic approaches are currently being tested using this rationale to improve responses to cancer immunotherapies. In this review, we discuss the immune mechanisms operating in viral infections, show evidence that exogenous viruses and endogenous retroviruses in cancer may enhance tumor immunogenicity, dissect the epigenetic control of EREs, and point to interferon pathway activation in the tumor milieu as a promising molecular predictive marker and immunotherapy target. Finally, we briefly discuss current strategies to modulate these responses within tumor tissues, including the clinical use of innate immune receptor agonists and DNA demethylating agents.
format	article
author	Glauco Akelinghton Freire Vitiello Wallax Augusto Silva Ferreira Wallax Augusto Silva Ferreira Vladmir Cláudio Cordeiro de Lima Tiago da Silva Medina Tiago da Silva Medina
author_facet	Glauco Akelinghton Freire Vitiello Wallax Augusto Silva Ferreira Wallax Augusto Silva Ferreira Vladmir Cláudio Cordeiro de Lima Tiago da Silva Medina Tiago da Silva Medina
author_sort	Glauco Akelinghton Freire Vitiello
title	Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
title_short	Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
title_full	Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
title_fullStr	Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
title_full_unstemmed	Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment
title_sort	antiviral responses in cancer: boosting antitumor immunity through activation of interferon pathway in the tumor microenvironment
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3427a3d049fa4ac3a23b500560336100
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Antiviral Responses in Cancer: Boosting Antitumor Immunity Through Activation of Interferon Pathway in the Tumor Microenvironment

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