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Updated: Jun 14, 2025
Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
Published on: March 7, 2025
Co-Occurring Infections in Cancer Patients Treated with Checkpoint Inhibitors Significantly Increase the Risk of
Siranuysh Grabska1,2, Hovakim Grabski1,2, Tigran Makunts1
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
Abstract:
Therapeutic antibodies designed to target three immune checkpoint proteins have been applied in the treatment of various malignancies, including small and non-small cell lung cancers, melanoma, renal cell carcinoma, and others. These treatments combat cancers by reactivating cytotoxic T cells. Nevertheless, this mode of action was found to be associated with a broad range of immune-related adverse events (irAEs), including pneumonitis, sarcoidosis, myocarditis, nephritis, colitis, and hepatitis. Depending on their severity, these irAEs often necessitate the suspension or discontinuation of treatment and, in rare instances, may lead to fatalities. We analyzed over nineteen million reports and identified over eighty thousand adverse event reports from patients treated with immune checkpoint inhibitors submitted to the Food and Drug Administration's Adverse Event Reporting System MedWatch. Reports concerning pembrolizumab, nivolumab, cemiplimab, avelumab, durvalumab, atezolizumab, and ipilimumab revealed a statistically significant association between the irAEs and concurrent infectious diseases for five out of seven treatments. Furthermore, the association trend was preserved across all three types of checkpoint inhibitors and each of the five individual therapeutic agent cohorts, while the remaining two showed the same trend, but an increased confidence interval, due to an insufficient number of records.
Insights
Immune checkpoint inhibitors treat cancer by reactivating T cells but can cause immune-related adverse events (irAEs). This study found a link between these irAEs and infections in patients receiving these cancer therapies.
Area of Science:
- Oncology
- Immunology
- Pharmacovigilance
Background:
- Immune checkpoint inhibitors (ICIs) target immune checkpoints to treat various cancers by reactivating cytotoxic T cells.
- While effective, ICIs are associated with immune-related adverse events (irAEs) such as pneumonitis, colitis, and hepatitis, which can be severe and even fatal.
Purpose of the Study:
- To investigate the association between immune-related adverse events (irAEs) and concurrent infectious diseases in patients treated with immune checkpoint inhibitors (ICIs).
Main Methods:
- Analysis of over 19 million adverse event reports from the FDA's MedWatch database, focusing on 80,000+ reports from patients treated with seven specific ICIs.
- Statistical analysis to identify significant associations between irAEs and infectious diseases across different ICI agents and classes.
Main Results:
- A statistically significant association between irAEs and concurrent infectious diseases was identified for five out of seven investigated immune checkpoint inhibitors.
- This association trend was consistent across all three types of checkpoint inhibitors and five individual therapeutic agents, despite variations in confidence intervals due to record numbers.
Conclusions:
- Concurrent infectious diseases may be significantly associated with the development of immune-related adverse events in patients undergoing treatment with immune checkpoint inhibitors.
- Further research is warranted to elucidate the mechanisms underlying this association and inform clinical management strategies.
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