Viral Pathogenesis in Cancer: Innate Immune Sensing, Interferon Pathways, and Immune Checkpoint Evasion

Virus-associated cancers are a significant and persistent global health challenge, providing unique insight into the relationship between chronic infection and the evasion of antitumor immunity. While the oncogenic potential of viruses like HPV and HBV is well-established, recent research has highlighted how persistent viral infections go beyond genomic alterations to transform the tumor microenvironment (TME). Central to this process are innate immune sensing pathways, particularly the cGAS–STING axis and related pattern-recognition receptor networks, which orchestrate type I and III interferon responses and shape inflammatory signaling within tumors. However, many virus-related cancers exhibit reprogrammed or subverted innate immune signaling, resulting in suppressed antigen presentation, exclusion of cytotoxic immune cells, dominant myeloid inflammation, and dysfunctional T cell responses. These changes have profound implications for the effectiveness of immunotherapies, especially since they intersect with key immune checkpoint pathways such as PD-1/PD-L1.This Research Topic aims to deepen mechanistic and translational understanding of how viral infection and antiviral innate immune sensing influence immune evasion and therapeutic outcomes in cancer. We seek to uncover how viral proteins and host pathways converge to regulate interferon-driven remodeling, immune checkpoint expression, and the resulting impact on the TME. The objective is to connect molecular events with clinical phenomena ranging from immunotherapy resistance to emerging prevention strategies, thereby fostering the development of new interventions, better biomarkers, and informed therapeutic combinations that target both viral and host determinants.The boundaries of this Research Topic focus on the mechanistic and functional links between viral pathogenesis, innate immunity, and immune escape in cancer, with clinical and translational perspectives prioritised. Descriptive studies without causal or molecular insights will not be considered. To gather further insights in virus-host dynamics and immunity-driven therapeutic responses, we welcome articles addressing, but not limited to, the following themes:(i) Viral modulation of cGAS–STING signaling and interferon programs in premalignant and tumor contexts (such as HPV- and HBV-associated malignancies);(ii) Mechanistic connections between innate antiviral signaling and checkpoint induction, T cell exhaustion, antigen presentation, and immune escape;(iii) Virus-driven cytokine/chemokine circuits controlling immune infiltration, myeloid polarization, and immune exclusion;(iv) Determinants of immunotherapy response and resistance in virus-associated cancers, including biomarker-guided translational studies with functional validation;(v) Translational and therapeutic advances informed by viral pathogenesis and host sensing, including development of antiviral agents, vaccines, and virus-based gene therapy vectors, as well as rational combinations that modulate innate immunity or checkpoints to improve antitumor efficacy. Topic editors: Tianye Li, Zizhuo Wang, Shihong Wu Source: https://www.frontiersin.org/research-topics/78844/viral-pathogenesis-in-cancer-innate-immune-sensing-interferon-pathways-and-immune-checkpoint-evasion