Prediction and treatment of skin adverse reactions related to inhibitors at immune checkpoints

Immunotherapy has become the fifth major treatment modality in oncology, with immune checkpoint inhibitors (ICIs) being the most effective immunotherapeutic agents currently used in clinical practice. Although the majority of patients exhibit good tolerance to ICIs, a subset of patients may develop severe immune-related adverse events (irAEs) following treatment. In this study, we included 47 cancer patients receiving PD-1 antibody therapy for the first time. By measuring cytokines in the patients' serum and performing single-cell RNA sequencing on immune cells from an in vitro co-culture system, our results indicated that elevated serum levels of IL-5 and IL-17, along with an increased proportion of PD-1 ⁺ CD4 ⁺ T cells, may be closely associated with the occurrence of skin irAEs. Transcriptomic analysis revealed that differentially expressed genes were enriched in the JAK-STAT signaling pathway, with a significant upregulation of inflammation-related proteins such as S100A8/A9. This study provides new insights into the early prediction and mechanistic understanding of skin irAEs, suggesting that monitoring serum cytokine levels and changes in immune cell subsets may help optimize ICI treatment strategies and reduce the occurrence of irAEs. Targeting key inflammatory pathways may offer novel therapeutic strategies for clinical management.