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PD ‐L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti‐ PD ‐1/ PD ‐ L 1 clinical trials

作者:Jason Madore, Ricardo E. Vilain, Alexander Maxwell Menzies, Hojabr Kakavand, James S. Wilmott, Jessica Hyman, Jennifer Holmes Yearley, Richard F. Kefford, John F. Thompson, Georgina Venetia Long, Peter Hersey, Richard A. Scolyer · 发表于:Pigment Cell & Melanoma Research · 年份:2014 · DOI:10.1111/pcmr.12340 · 被引用次数:399 · 研究领域:Cancer Immunotherapy and Biomarkers、CAR-T cell therapy research、Immunotherapy and Immune Responses

This study evaluated the expression of PD-L1 in immunotherapy-naïve metastatic melanoma patients to determine longitudinal intrapatient concordance and correlate PD-L1 status with clinicopathologic characteristics and outcome. PD-L1 expression was assessed by immunohistochemistry in 58 patients (43 primary tumors, 96 metastases). Seventy-two percent of patients had at least one specimen expressing PD-L1 in ≥ 1% of tumor cells. Median positive tumor cell count overall was low (8% in nonzero specimens). PD-L1 expression was frequently discordant between primary tumors and metastases and between intrapatient metastases, such that 23/46 longitudinal patient specimens were discordant. PD-L1 was associated with higher TIL grade but not with other known prognostic features. There was a positive univariate association between PD-L1 expression in locoregional metastases and melanoma-specific survival, but the effect was not observed for primary melanoma. In locoregional lymph node metastasis, PD-L1+/TIL+ patients had the best outcome, and PD-L1+/TIL- patients had poor outcome.