Immune-Related Adverse Events in Cancer Therapy

Immune-related adverse events (irAEs) are unintended inflammatory reactions triggered by therapies that enhance the body’s immune response against tumours. As immune checkpoint inhibitors have revolutionised treatment for many malignancies, irAEs have emerged as a pivotal concern in clinical practice. These toxicities may affect any organ system, with skin, gastrointestinal tract, endocrine glands, liver and lungs most commonly involved. Their onset can range from days to months after therapy initiation, and severity spans from mild, self-limited symptoms to life-threatening complications. The mechanisms underpinning irAEs reflect the complexity of immune regulation, involving off-target T-cell activation, cytokine dysregulation and disruption of peripheral tolerance. Early recognition and prompt management with immunosuppressive agents such as corticosteroids or targeted biologics are essential to balance anti-tumour efficacy with patient safety. With expanding indications for checkpoint blockade across diverse cancers and combination regimens, understanding irAE risk factors, biomarkers and pathobiology is critical for optimising outcomes and informing rechallenge strategies.

Research from Nature Portfolio

Single-cell transcriptomic analyses have revealed the expansion of IL1Bhi macrophages in peripheral blood and synovial fluid of patients developing inflammatory arthritis during PD-1 blockade. These myeloid cells exhibit heightened NLRP3 inflammasome activity and engage with exhausted CD8+ T-cell subsets via chemokine-receptor axes, identifying potential targets for intervention. Separately, a multi-omics approach integrating pharmacovigilance and genomic data pinpointed two metabolic genes whose expression correlates with reporting rates of irAEs across cancer types. A bivariate regression model incorporating these biomarkers demonstrated predictive power in an independent cohort, offering a framework for early risk stratification and personalised monitoring.

Immune-Related Adverse Events in Cancer Therapy publication trend

The graph below shows the total number of articles in immune-related adverse events in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitors (ICIs): Monoclonal antibodies that block regulatory receptors on T cells to enhance anti-tumour immunity.

Immune-related adverse events (irAEs): Inflammatory toxicities arising from off-target immune activation during cancer immunotherapy.

Single-cell RNA sequencing: A method to profile gene expression in individual cells, revealing cellular heterogeneity and specific disease mechanisms.

Inflammasome: A multiprotein complex in myeloid cells that activates inflammatory cytokines such as interleukin-1β.

Cytokine: A secreted protein that mediates communication between immune cells and regulates inflammation.

Biomarker: A measurable molecular indicator used to predict, diagnose or monitor disease or treatment effects.

Rechallenge: The resumption of immunotherapy after interruption due to adverse events, often with prophylactic measures.

References

1. Single-cell profiling identifies IL1Bhi macrophages associated with inflammation in PD-1 inhibitor-induced inflammatory arthritis. Nature Communications (2024).
2. Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy. Nature Communications (2020).
3. Tocilizumab provides dual benefits in treating immune checkpoint inhibitor-associated arthritis and preventing relapse during ICI rechallenge: the TAPIR study. Annals of Oncology (2024).
4. Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors. Frontiers in Immunology (2022).