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

Author(s)

Vitiello, Glauco Akelinghton Freire ^[1] ; Ferreira, Wallax Augusto Silva ^{[1, 2]} ; Cordeiro de Lima, Vladmir Claudio ^[3] ; Medina, Tiago da Silva ^{[4, 1]}

Affiliation

^[1] AC Camargo Canc Ctr, Int Res Ctr, Translat Immunooncol Grp, Sao Paulo - Brazil

^[2] Evandro Chagas Inst, Lab Cytogen & Environm Mutagenesis, Environm Sect SAMAM, Ananindeua - Brazil

^[3] AC Camargo Canc Ctr, Dept Clin Oncol, Sao Paulo - Brazil

^[4] Natl Inst Sci & Technol Oncogen & Therapeut Innov, Sao Paulo - Brazil

• Document type: Review article
• Source: FRONTIERS IN IMMUNOLOGY; v. 12, DEC 2 2021.
• Web of Science Citations: 0

Abstract

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. (AU)

• FAPESP's process: 20/10299-7 - PIWIL4 as a central regulator of endogenous retroviral elements in Gastric Cancer: implications for immunopathogenesis and immunotherapy?
• Grantee: Glauco Akelinghton Freire Vitiello
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/50943-1 - INCT 2014: on Oncogenomics and Therapeutic Inovations
• Grantee: Dirce Maria Carraro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/14034-8 - Characterization of chromatin and transcriptional landscapes of T cells from gastric adenocarcinoma patients as a tool to discover immunotherapy targets
• Grantee: Tiago da Silva Medina
• Support Opportunities: Research Grants - Young Investigators Grants