Objective:

To systematically summarize the clinical application of immune checkpoint inhibitors (ICIs) across different viral infection backgrounds and highlight recent advances in underlying immunological mechanisms, using a structured approach.

Key Findings:

• Viral infections like HBV, HCV, HIV, HPV, and EBV significantly influence the efficacy and safety of ICIs, with nuanced effects on treatment outcomes.
• Patients with concurrent viral infections may experience enhanced antitumor immune function and potential virological responses when treated with ICIs, though individual responses can vary.
• The risk of viral reactivation is a concern, particularly in the context of immune-related adverse events (irAEs), necessitating careful monitoring.
• HPV-positive patients show higher objective response rates and extended overall survival with ICIs, indicating a potential biomarker for treatment efficacy.

Interpretation:

The interplay between viral infections and the immune response can lead to both enhanced therapeutic outcomes and increased risks, necessitating careful management in cancer immunotherapy, particularly in tailoring treatment strategies.

Limitations:

• Existing literature lacks systematic integration of virus–immunity–cancer interactions from a pan-viral perspective, highlighting the need for comprehensive future studies.
• There is a need for more comprehensive comparisons of mechanisms, therapeutic variations, and safety profiles across different viral contexts to inform clinical practice.

Conclusion:

Optimizing the integration of ICIs and antiviral therapies is crucial for improving treatment strategies in patients with virus-associated malignancies, particularly through personalized approaches.