With recent approval of inhibitors of PD-1 in melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC), extensive efforts are underway to develop biomarkers predictive of response. PD-L1 expression has been most widely studied, and is more predictive in NSCLC than RCC or melanoma. We therefore studied differences in expression patterns across tumor types.
We employed tissue microarrays with tumors from NSCLC, RCC 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.
PD-L1 expression was higher in NSCLC specimens than RCC, 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 multi-variable analysis.
PD-L1 expression in melanoma tumor cells is lower than NSCLC or RCC 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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2017 Feb 21 [Epub ahead of print]
Harriet M Kluger, Christopher R Zito, Gabriela Turcu, Marina Baine, Hongyi Zhang, Adebowale Adeniran, Mario Sznol, David L Rimm, Yuval Kluger, Lieping Chen, Justine V Cohen, Lucia B Jilaveanu
Medical Oncology, Yale University School of Medicine ., Department of Biology, School of Health and Natural Sciences, University of Saint Joseph., Department of Dermatology, Carol Davila University of Medicine and Pharmacy., Yale Cancer Center, Yale University., Department of Medicine, Yale University School of Medicine., Department of Pathology, Yale University School of Medicine., Section of Medical Oncology, Yale University School of Medicine., Immunobiology, Yale University School of Medicine., Department of Medicine, Section of Medical Oncology, Yale University School of Medicine.