Immunotherapy Impacts on Viral Infections in Cancer Patients

Immune checkpoint inhibitors and related immunotherapies have transformed cancer treatment by reinvigorating antitumour T cell responses. However, their use in patients harbouring chronic or acute viral infections raises complex challenges. On one hand, enhanced T cell activation may suppress viral persistence and improve oncological outcomes; on the other, it can precipitate viral reactivation or exacerbate immune‐mediated toxicity. Evidence to date spans diverse pathogens—including hepatitis B and C viruses, human immunodeficiency virus, influenza and emerging agents such as SARS-CoV-2—and suggests that, with careful monitoring and antiviral prophylaxis where indicated, most patients can derive anticancer benefit without uncontrolled viral replication. Yet key uncertainties remain regarding optimal vaccine timing, the interplay between antiviral therapy and immune‐mediated adverse events, and the exclusion of certain patient groups from pivotal clinical trials. A nuanced understanding of these interdependencies is essential to broaden safe access to immunotherapy and to harness its potential to modulate both tumour and viral immunity.

Research from Nature Portfolio

Despite growing evidence that immune checkpoint inhibitors can be both safe and effective in people living with chronic viral infections, the majority of contemporary clinical trials continue to exclude those with well-controlled HIV. A recent analysis of trial protocols revealed that over 70 percent of studies screen out people living with HIV or impose conditional criteria that restrict enrolment to those with normal CD4+ T cell counts. This persistent exclusion hinders the generation of prospective safety and efficacy data and underscores the need for more inclusive trial designs to inform clinical practice across diverse patient populations.

Immunotherapy Impacts on Viral Infections in Cancer Patients publication trend

The graph below shows the total number of articles in immunotherapy impacts on viral infections in cancer patients across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitor: A therapeutic antibody that blocks regulatory receptors on T cells to enhance antitumour immunity.

Programmed death receptor-1 (PD-1): An inhibitory receptor on T cells whose blockade can restore immune activity against cancer and chronic infections.

Immune-related adverse event (irAE): An unintended inflammatory toxicity arising from heightened immune activation during immunotherapy.

Viral reactivation: The resurgence of viral replication from a latent or controlled state, often triggered by immunomodulation.

T cell exhaustion: A dysfunctional state of T cells characterised by up-regulation of inhibitory receptors, reduced cytokine production and impaired cytotoxicity.

References

1. Anti-PD-1 therapy achieves favorable outcomes in HBV-positive non-liver cancer. Oncogenesis (2023).
2. Hepatitis B virus reactivation in cancer patients with positive Hepatitis B surface antigen undergoing PD-1 inhibition. Journal for ImmunoTherapy of Cancer (2019).
3. Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events. Journal for ImmunoTherapy of Cancer (2018).
4. Safety and efficacy of immune checkpoint inhibitors (ICIs) in cancer patients with HIV, hepatitis B, or hepatitis C viral infection. Journal for ImmunoTherapy of Cancer (2019).
5. On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19. Journal for ImmunoTherapy of Cancer (2020).
6. Exclusion of patients living with HIV from cancer immune checkpoint inhibitor trials. Scientific Reports (2021).