Journal
CLINICAL CANCER RESEARCH
Volume 21, Issue 13, Pages 3052-3060Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-14-3073
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Funding
- NIH [R0-1 CA158167, K24CA172123]
- Yale SPORE in Skin Cancer [P50 CA121974]
- Yale Cancer Center
- CTSA Grant from the National Center for Research Resources (NCRR) [KL2 TR000140]
- National Center for Advancing Translational Science (NCATS), NIH
- NIH roadmap for Medical Research
- Lung Cancer Research Foundation LUNGevity
- Melanoma Research Alliance [308721]
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Purpose: Programmed death ligand-1 (PD-L1) tumor expression represents a mechanism of immune escape for melanoma cells. Drugs blocking PD-L1 or its receptor have shown unprecedented activity in melanoma, and our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in metastatic melanomas. Experimental Design: We used a tissue microarray (TMA) consisting of two cores from 95 metastatic melanomas characterized for clinical stage, outcome, and anatomic site of disease. We assessed PD-L1 expression and tumor-infiltrating lymphocyte (TIL) content (total T cells and CD4/CD8 subsets) by quantitative immunofluorescence. Results: High PD-L1 expression was associated with improved survival (P = 0.02) and higher T-cell content (P = 0.0005). Higher T-cell content (total and CD8 cells) was independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extracerebral metastases was associated with increased time to developing brain metastases (P = 0.03). Cerebral and dermal metastases had slightly lower PD-L1 expression than other sites, not statistically significant. Cerebral metastases had less T cells (P = 0.01). Conclusions: T-cell-infiltrated melanomas, particularly those with high CD8 T-cell content, are more likely to be associated with PD-L1 expression in tumor cells, an improved prognosis, and increased time to development of brain metastases. Studies of T-cell content and subsets should be incorporated into trials of PD-1/PD-L1 inhibitors to determine their predictive value. Furthermore, additional studies of anatomic sites with less PD-L1 expression and T-cell infiltrate are needed to determine if discordant responses to PD-1/PD-L1 inhibitors are seen at those sites. (C) 2015 AACR.
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