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Clin Cancer Res. 2017 Aug 1;23(15):4270-4279. doi: 10.1158/1078-0432.CCR-16-3146. Epub 2017 Feb 21.

PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors.

Author information

1
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut. harriet.kluger@yale.edu.
2
Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, Connecticut.
3
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
4
Department of Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
5
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
6
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.

Abstract

Purpose: With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma, extensive efforts are under way to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than renal cell carcinoma or melanoma. We therefore studied differences in expression patterns across tumor types.Experimental Design: We used tissue microarrays with tumors from NSCLC, renal cell carcinoma, or melanoma and a panel of cell lines to study differences between tumor types. Predictive studies were conducted on samples from 65 melanoma patients treated with PD-1 inhibitors alone or with CTLA-4 inhibitors, characterized for outcome. PD-L1 expression was studied by quantitative immunofluorescence using two well-validated antibodies.Results: PD-L1 expression was higher in NSCLC specimens than renal cell carcinoma, and lowest in melanoma (P = 0.001), and this finding was confirmed in a panel of cell lines. In melanoma tumors, PD-L1 was expressed either on tumor cells or immune-infiltrating cells. The association between PD-L1 expression in immune-infiltrating cells and progression-free or overall-survival in melanoma patients treated with ipilimumab and nivolumab was stronger than PD-L1 expression in tumor cells, and remained significant on multivariable analysis.Conclusions: PD-L1 expression in melanoma tumor cells is lower than NSCLC or renal cell carcinoma cells. The higher response rate in melanoma patients treated with PD-1 inhibitors is likely related to PD-L1 in tumor-associated inflammatory cells. Further studies are warranted to validate the predictive role of inflammatory cell PD-L1 expression in melanoma and determine its biological significance. Clin Cancer Res; 23(15); 4270-9. ©2017 AACR.

PMID:
28223273
PMCID:
PMC5540774
DOI:
10.1158/1078-0432.CCR-16-3146
[Indexed for MEDLINE]
Free PMC Article

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