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Published on: April 13, 2015
Changes of peripheral T cell subsets in melanoma patients with immune-related adverse events
Benjamin Müller1, Anne Bärenwaldt1, Petra Herzig1
1Laboratory for Cancer Immunotherapy and Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.
Introduction:
Immunotherapies have improved the prognosis of many cancer patients including patients with advanced melanoma. Immune checkpoint receptors including CTLA-4 and PD-1 have been established as main therapeutic targets for immunotherapy of melanoma. Although monotherapy is effective in melanoma patients, a dual therapy approach has been shown to be most effective. Dual checkpoint blockade, however, increases substantially the risk for immune-related adverse events (irAEs).
Methods:
In this study, we characterized peripheral immune cell subsets in patients with anti-PD-1 monotherapy and with dual immune receptors blockade targeting PD-1 and CTLA-4.
Results:
We found differences in peripheral T cells between patients who developed severe immune-related side effects and patients with mild irAEs. We identified several mainly changes in CD8+ T cell subsets in patients with severe irAE under dual PD-1 and CTLA-4 blockade.
Discussion:
This work suggests that peripheral immune cell dynamics could be associated with severe immune-related side effects in patients receiving immune checkpoint inhibitors. These changes could be used as future biomarkers in early diagnosis of irAEs.
Insights
Dual immune checkpoint blockade for melanoma increases side effects. Researchers identified specific peripheral T cell changes in patients experiencing severe immune-related adverse events (irAEs), suggesting potential biomarkers for early diagnosis.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Immunotherapy, particularly targeting immune checkpoint receptors like CTLA-4 and PD-1, has significantly improved outcomes for cancer patients, especially those with advanced melanoma.
- While monotherapy is effective, dual checkpoint blockade (targeting both PD-1 and CTLA-4) offers superior efficacy but carries a higher risk of immune-related adverse events (irAEs).
Purpose of the Study:
- To characterize peripheral immune cell subsets in melanoma patients undergoing anti-PD-1 monotherapy versus dual PD-1 and CTLA-4 blockade.
- To identify immune cell differences associated with the severity of immune-related adverse events (irAEs) in patients receiving dual immune checkpoint blockade.
Main Methods:
- Peripheral blood samples were collected from melanoma patients treated with either anti-PD-1 monotherapy or dual PD-1/CTLA-4 blockade.
- Immune cell subsets were analyzed to identify differences between patients with mild versus severe irAEs.
Main Results:
- Significant differences were observed in peripheral T cell subsets between patients who developed severe irAEs and those with mild irAEs.
- Specific alterations in CD8+ T cell subsets were identified in patients experiencing severe irAEs under dual PD-1 and CTLA-4 blockade.
Conclusions:
- Peripheral immune cell dynamics are potentially associated with the development of severe irAEs in patients treated with immune checkpoint inhibitors.
- These immune cell changes may serve as valuable biomarkers for the early diagnosis of irAEs, enabling timely intervention and management.
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