# Chronic viral infections and their role in shaping the tumor immune microenvironment

## TL;DR

Chronic viral infections like HBV and HCV shape the tumor immune environment, promoting cancer growth and metastasis through immune suppression and altered signaling pathways.

## Contribution

The paper identifies key immunoregulatory mechanisms and signaling pathways linking chronic viral infections to tumor progression and metastasis.

## Key findings

- Chronic viruses promote tumor growth by increasing immunosuppressive cells and cytokines.
- Viruses activate pathways like NF-κB and PD-1/PD-L1 to support tumor survival and metastasis.
- Combining antiviral therapy with immune checkpoint inhibitors may improve outcomes in virus-related cancers.

## Abstract

Chronic viral infections, such as HBV, HCV, EBV, and HPV, contribute to tumorigenesis not only through direct oncogenic effects but also by reshaping the tumor immune microenvironment (TIME) via complex immunoregulatory mechanisms. These infections enhance immune suppression and promote metastasis. Viruses induce the accumulation of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and immunosuppressive cytokines, while driving CD8+ T cell exhaustion and impairing NK cell function, creating an immune environment favorable for tumor survival. Chronic inflammation, pro-angiogenic factors, and signals mediated by exosomes and microvesicles further remodel local and distant microenvironments, forming a “pre-metastatic niche” that supports tumor cell colonization and metastasis. Key signaling pathways, including NF-κB, STAT3, PD-1/PD-L1, and TGF-β, are persistently activated by viral proteins such as HBx and LMP1, reinforcing immunosuppression and metastasis. Based on these mechanisms, combined strategies of antiviral therapy with immune checkpoint inhibitors (ICIs) or targeting exosomes and immunosuppressive pathways show potential to enhance antitumor immunity and limit metastasis. A deeper understanding of the virus-immune-metastasis axis and related biomarkers may provide precise immunotherapeutic strategies for virus-associated cancers and improve patient outcomes.