PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E mutation.

Abstract

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 IFNγ. Melanomas express PD-L1 in association with tumor-infiltrating lymphocytes (TIL), 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 assessed for PD-L1 expression, TIL infiltration, and BRAFmut simultaneously. IFNγ-induced PD-L1 expression in cultured melanomas was assessed in parallel according to BRAF status. Melanocyte PD-L1 expression was observed in 40% of specimens, and BRAFmut was observed in 42% of specimens, but no significant concordance was found between these variables. Almost all melanocytes displaying PD-L1 expression were observed to be adjacent to TILs, irrespective of BRAF status. TIL(-) lesions were not more likely to be associated with BRAFmut, when compared with TIL(+) lesions. Baseline expression of PD-L1 by melanoma cell lines was virtually nil, regardless of BRAFmut status, and the intensity of IFN-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 versus PD-1 pathway blockade.

• Authors: Nemanja Rodić, Robert A Anders, James R Eshleman, Ming-Tseh Lin, Haiying Xu, Jung H Kim, Katie Beierl, Shuming Chen, Brandon S Luber, Hao Wang, Suzanne L Topalian, Drew M Pardoll, Janis M Taube
• Journal: Cancer immunology research (Cancer Immunol Res) Vol. 3 Issue 2 Pg. 110-5 (Feb 2015) ISSN: 2326-6074 [Electronic] United States
• PMID: 25370533 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2014 American Association for Cancer Research.

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Neoplasm Proteins
• Interferon-gamma
• BRAF protein, human
• Proto-Oncogene Proteins B-raf

Topics

• B7-H1 Antigen (metabolism)
• Humans
• Interferon-gamma (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Melanocytes (immunology)
• Melanoma (genetics, immunology, secondary)
• Mutation
• Neoplasm Proteins (genetics, metabolism)
• Nevus (genetics, immunology)
• Proto-Oncogene Proteins B-raf (genetics)
• Tumor Cells, Cultured