Characterization of PD-L1 Expression and Associated T-cell Infiltrates in Metastatic Melanoma Samples from Variable Anatomic Sites

被引:173
作者
Kluger, Harriet M. [1 ]
Zito, Christopher R. [2 ]
Barr, Meaghan L. [1 ]
Baine, Marina K. [1 ]
Chiang, Veronica L. S. [3 ]
Sznol, Mario [1 ]
Rimm, David L. [4 ]
Chen, Lieping [5 ]
Jilaveanu, Lucia B. [1 ]
机构
[1] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA
[2] Univ St Joseph, Sch Hlth & Nat Sci, Dept Biol, Hartford, CT USA
[3] Yale Univ, Sch Med, Dept Neurosurg & Therapeut Radiol, New Haven, CT 06520 USA
[4] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA
[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
关键词
CANCER; SAFETY; APOPTOSIS; RESPONSES; ANTI-PD-1; BLOCKADE; EFFECTOR; ANTIBODY; BRAIN;
D O I
10.1158/1078-0432.CCR-14-3073
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3052 / 3060
页数:9
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