Work

Activation of endogenous retroviruses in tumor cells and their immunomodulatory mechanisms: from molecular basis to clinical translation

Year: 2026

Type: article

Abstract: Endogenous retroviruses (ERVs), regarded as "molecular fossils" embedded within the human genome, have been shown to exhibit increasingly intimate associations with tumor initiation, progression, and immune evasion through aberrant activation events. This review aims to systematically dissect the molecular mechanisms underlying ERV reactivation in the tumor microenvironment (TME), which are mediated by epigenetic reprogramming, transcription factor network dysregulation, and genomic instability, while highlighting their dual role in immune modulation. On one hand, ERVs activate innate and adaptive antitumor immunity via "viral mimicry" responses; on the other hand, they can induce the expression of immune checkpoint molecules and foster an immunosuppressive TME, thereby facilitating tumor immune evasion. Leveraging recent advancements in single-cell multi-omics and spatial transcriptomics technologies, this review delineates the dynamic expression patterns of ERVs in tumor heterogeneity and integrates extensive preclinical and clinical trial data to illustrate the translational potential of ERV-targeted strategies in tumor diagnosis, prognostic assessment, and immunotherapy. Finally, this review proposes addressing current research bottlenecks by harnessing spatiotemporally precise gene-editing technologies and AI-driven ERV activity prediction models, thus offering a novel paradigm for the development of next-generation tumor immunotherapies.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2026.1752231

Authors: Jintong Zhang, Yanhua Zhang, Xiaochun Peng

Institution: Yangtze University

Language: English

Topic: Cancer Immunotherapy and Biomarkers

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801