Targeting archetypes of viral-driven cancers with immunotherapy: a perspective on immunogenicity within the tumor microenvironment

Front Immunol. 2025 Aug 29:16:1631258. doi: 10.3389/fimmu.2025.1631258. eCollection 2025.

Abstract

Viral etiologies of cancers have been widely studied for tumorigenesis and in recent years, widely recognized for their potential influence on immune regulation and response to immune checkpoint blockade (ICB). Here, we review the current understanding of how various oncogenic viruses are related to tumor immunogenicity and the tumor immune microenvironment. The present work also highlights the distinct features of these viral-driven cancers, that can be largely prognostic for better patient survival and response to ICB. On the other hand, there are also several commonalities in which these cancers acquire resistance against conventional immunotherapy. Finally, we discuss our perspectives to address the existing conundrums to gain clearer insights on how the interplay between anti-viral and anti-tumor immunity can be exploited to develop novel therapeutic interventions.

Keywords: immune check inhibitor (ICI); immunogenicity; immunotherapy; tumor microenvironment (TME); viral-driven cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / methods
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Neoplasms* / virology
  • Oncogenic Viruses* / immunology
  • Tumor Microenvironment* / immunology
  • Tumor Virus Infections* / immunology
  • Tumor Virus Infections* / therapy

Substances

  • Immune Checkpoint Inhibitors