Characterization of PD-L1 Expression and Associated T cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites
A partir d'échantillons tumoraux prélevés sur 95 patients atteints d'un mélanome métastatique, cette étude évalue l'association entre l'expression de PD-L1, le nombre de lymphocytes infiltrant les tumeurs et la survie des patients
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 lymphocytes (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) were independently associated with improved overall survival; PD-L1 expression was not independently prognostic. High TIL content in extra-cerebral 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.
Clinical Cancer Research , résumé, 2015