Cancer‐Associated Fibroblast Signature Can Predict Prognosis and Therapeutic Responses in Skin Cutaneous Melanoma

ABSTRACT Skin cutaneous melanoma (SKCM) is a lethal skin cancer with a poor prognosis and limited response to immunotherapy. Cancer‐associated fibroblasts (CAFs) are key contributors to tumor progression, therapy resistance, and immunosuppression. In this study, mRNA sequencing and clinical data from SKCM samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to evaluate the prognostic significance, therapeutic implications, and potential for enhancing immunotherapy through targeting CAFs in SKCM. A CAF‐related risk model comprising nine genes was developed, revealing that patients classified as low‐risk exhibited superior survival outcomes and increased sensitivity to immunotherapy. Spearman correlation analysis identified significant associations between the risk score and the sensitivity to 40 drugs, as well as resistance to 17 drugs. Additionally, CAFs were categorized into three distinct subgroups in SKCM, with antigen‐presenting CAFs (apCAFs) notably suppressing the infiltration of anti‐tumor immune cells and strongly correlating with poor prognosis. In summary, the CAF‐related risk model offers a robust prognostic tool for SKCM, capable of predicting both survival outcomes and therapeutic sensitivity. Moreover, the pivotal role of apCAFs within the immune microenvironment suggests that targeting these cells may enhance the efficacy of immunotherapy.