Expression of DNA mismatch repair proteins in melanoma patients treated with immune checkpoint inhibitors

Purpose To investigate the protein expression of DNA mismatch repair (MMR) proteins in patients with cutaneous melanoma (CM) under immune checkpoint inhibitor (ICI) therapy. Methods Immunohistochemistry was performed on tumor tissue for MMR proteins MLH1, MSH2, MSH6, and PMS2 in 50 metastatic CM patients treated with ICI (ipilimumab, nivolumab, pembrolizumab). Results Best overall response (BOR) rate was 48% (24/50). Reduced MMR protein expression (nuclear expression in < 80% of tumor cells) was observed in 8 patients (16%). Compared to other clinical parameters, baseline neutrophil/lymphocyte ratio and reduced intratumoral MMR protein expression (P = 0.0033) were determined as the only parameters significantly associated with favorable BOR. However, in this small study population, reduced MMR protein expression did not reach statistical significance in multivariate analysis. Conclusion Reduced MMR protein expression is observed in CM and might predict favorable BOR in patients treated with ICI, as was observed for other entities. However, these findings need to be substantiated in larger patient cohorts.

Automated summary

The study investigated the protein expression of DNA mismatch repair (MMR) proteins in patients with cutaneous melanoma (CM) receiving immune checkpoint inhibitor (ICI) therapy. Immunohistochemistry was performed on tumor tissue of 50 patients, and reduced MMR protein expression was observed in 16% of patients. Baseline neutrophil/lymphocyte ratio and reduced intratumoral MMR protein expression were significantly associated with favorable treatment response. However, further validation is required in larger patient cohorts.