Viruses in the tumor immune microenvironment: implications for immunotherapy

The intricate interplay between viruses and the tumor immune microenvironment (TIME) plays a pivotal role in tumor initiation, progression, and response to immunotherapy. Viruses can directly infect tumor cells, modulate immune cell functions, and reshape cytokine networks, thereby influencing the composition and functionality of the TIME. This review systematically examines how viral infections impact TIME by altering tumor-infiltrating lymphocytes, cytokine profiles, and immune checkpoint expression. Additionally, the role of virus-associated antigens as immune targets and the mechanisms of virus-induced immune evasion that undermine immunotherapeutic efficacy are discussed. By integrating recent advances from single-cell omics, spatial transcriptomics, and clinical studies, this article aims to elucidate the core mechanisms underlying virus-TIME interactions. Furthermore, it highlights the therapeutic potential and challenges of virus-based immunotherapies, including oncolytic virotherapy and viral vector vaccines. This comprehensive overview provides a theoretical foundation for optimizing immunotherapeutic strategies that leverage viral components to enhance anti-tumor immunity and overcome immune resistance.