PD-L1 expression in melanoma correlates with response to PD-1 pathway blocking antibodies. Aberrant tumor cell PD-L1 expression may be oncogene-driven and/or induced by interferon-gamma (IFN-g). Melanomas express PD-L1 in association with tumor infiltrating lymphocytes (TILs), but the potential contribution of the BRAF V600E mutation (BRAFmut) to induced PD-L1 expression has not been determined. Fifty-two archival melanocytic lesions were simultaneously assessed for PD-L1 expression, TIL infiltration and BRAFmut. IFN-g-induced PD-L1 expression in cultured melanomas was also assessed according to BRAF status. Melanocyte PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in 42% of specimens, but there was no significant concordance between these variables. Almost all melanocytes displaying PD-L1 expression were observed adjacent to TILs, irrespective of BRAF status. TIL(-) lesions were not more likely to be associated with BRAFmut, compared to TIL(+) lesions. Baseline expression of PD-L1 by melanoma cell lines was virtually nil regardless of BRAFmut status, and the intensity of interferon-induced PD-L1 expression in melanoma cell lines likewise did not correlate with BRAF mutational status. PD-L1 expression in melanocytic lesions does not correlate with the BRAFmut. Thus, distinct populations of melanoma patients will likely benefit from BRAF inhibitors vs. PD-1 pathway blockade.
- Received August 8, 2014.
- Revision received October 5, 2014.
- Accepted October 26, 2014.
- Copyright © 2014, American Association for Cancer Research.