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Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized
Mario E Lacouture1, Elena Goleva2, Neil Shah3
1Dermatology Service, Division of Subspecialty Medicine, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Summary
Immune-related skin reactions to checkpoint inhibitors have distinct immune profiles. Identifying these endotypes can guide precision medicine for better treatment outcomes.
Area of Science:
- Dermatology
- Immunology
- Oncology
Background:
- Immune-related cutaneous adverse events (ircAEs) affect over 50% of patients on checkpoint inhibitors.
- The underlying mechanisms of ircAEs remain poorly understood, hindering effective management.
Purpose of the Study:
- To characterize the clinical presentation and immunologic endotypes of ircAEs.
- To identify distinct cytokine profiles associated with specific ircAE phenotypes.
Main Methods:
- Phenotyping and biomarker analyses were performed on 200 patients receiving checkpoint inhibitors.
- Cytokine levels were measured in skin biopsies, tape strips, and plasma using real-time PCR and multiplex assays.
Main Results:
- Eight distinct ircAE phenotypes were identified, including maculopapular rash, eczema, and lichenoid dermatitis, all showing skin lymphocyte and eosinophil infiltrates.
- Specific cytokine profiles correlated with phenotypes: IFNγ in lichenoid/psoriasiform, IL13 in eczema, and IL17A in psoriasiform/lichenoid/bullous dermatitis/MPR.
- Distinct cytokine patterns were observed across skin and plasma, with type 1/17 pathway activation in psoriasiform, lichenoid, bullous dermatitis, and vitiligo.
Conclusions:
- Distinct immunologic endotypes of ircAEs were identified.
- These findings suggest potential actionable targets for precision medicine interventions in managing ircAEs.
