CARD11 alteration as a candidate biomarker of skin cutaneous melanoma treated with immune checkpoint blockade.

Background Immune checkpoint inhibitors (ICIs) can be problematic, including a lack of sustained clinical response, in the treatment of skin cutaneous melanoma (SKCM) patients; therefore, predictive biomarkers are urgently needed. Recently, gene mutations identified by melanoma genomic analysis have shown great predictive potential. Methods We collected an immunotherapy cohort and The Cancer Genome Atlas (TCGA)-SKCM cohort from published studies and tested the predictive function of the CARD11 mutation. We then further studied the association between the CARD11 mutation and tumor immunogenicity by studying related genes and pathways in the tumor microenvironment (TME). Results In the immunotherapy and TCGA-SKCM cohorts, patients with CARD11-mutant (MT) tumors had longer overall survival (OS) and a better prognosis than those with CARD11-wild-type (WT) tumors. CARD11-MT tumors had higher immunogenicity, and gene expression related to immunosuppression was significantly downregulated in CARD11-MT tumors. We found that immunosuppression-related pathways were significantly downregulated in CARD11-MT tumors, while immune activation-related pathways were significantly upregulated. Additionally, CARD11-MT tumors had more DNA damage response and repair (DDR) pathway mutations. Conclusions CARD11 mutation is associated with longer OS and a better prognosis after ICI treatment. Therefore, the CARD11 gene can be used as a biomarker for predicting the efficacy of ICIs in SKCM patients.