Melanoma response to immune therapy

Anti-PD-1 therapy – a treatment that stimulates the immune system to attack tumors – produces responses in up to 40 percent of melanoma patients. Predictive markers of response are needed to optimize patient selection, improve treatment decision-making and minimize costs.

Justin Balko, Pharm.D., Ph.D., Douglas Johnson, M.D., and colleagues hypothesized that tumor expression of MHC-I and -II – proteins that “mark” tumor cells as targets for immune attack – may predict anti-PD-1 therapy response. Across 60 melanoma cell lines, the investigators found that MHC-II expression varied, while MHC-I expression was ubiquitous.

In two cohorts of melanoma patients treated with anti-PD-1 therapy, MHC-II expression on tumor cells was associated with therapeutic response, progression-free and overall survival.

These findings, reported in Nature Communications, show that melanoma-specific expression of the MHC-II protein HLA-DR identifies tumors that are more responsive to PD-1-targeted therapy. The authors propose using HLA-DR expression as a biomarker for response to anti-PD-1 therapies.

This research was supported in part by the National Institutes of Health (grants CA181491, CA090652).