Send to

Choose Destination
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

Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Biology, School of Health and Natural Sciences, University of Saint Joseph, West Hartford, Connecticut.
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
Department of Dermatology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut.


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.

[Indexed for MEDLINE]
Free PMC Article

MeSH terms, Substances, Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center