MHC class II: a predictor of outcome in melanoma treated with immune checkpoint inhibitors

This study aimed to evaluate the predictive value of MHC class II (MHC-II) expression by melanoma cells in a large cohort of metastatic cutaneous melanoma patients treated with immune checkpoint inhibitors (ICIs). We conducted a single-center, retrospective study involving stage IV cutaneous melanoma patients who received ICI as first-line therapy. MHC-II expression in melanoma cells was quantified using dual-color anti-SOX10 and anti-MHC-II immunohistochemistry on tumor samples from 95 patients. The primary endpoint was event-free survival (EFS), with secondary endpoints including 1-year EFS, 1-year overall survival (OS), disease control rate (DCR), and the correlation between MHC-II expression and clinico-biological characteristics. The cohort had a median age of 67 years (range, 33-90), with a male-to-female ratio of 50 : 45. Thirty-three percent of patients received the ipilimumab-nivolumab combination. The median follow-up was 16.8 months. Disease progression occurred in 58 patients (61%), with a median time to progression of 4.8 months. Forty-six patients (48.4%) experienced an event within the first year, and 52 patients (54.7%) died during follow-up. MHC-II positivity was observed in ≥10% of melanoma cells in 6.3% of patients. MHC-II expression was significantly associated with 1-year EFS ( P  = 0.037) and DCR ( P  = 0.032), but not with EFS or 1-year OS. Age, phototype, and brain metastases were correlated with MHC-II expression status. Our findings suggest that MHC-II expression by melanoma cells may serve as a favorable predictive biomarker for survival in metastatic cutaneous melanoma patients treated with ICIs.