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

• Published in: Pigment cell and melanoma research Vol. 28; no. 3; pp. 245 - 253
• Main Authors: Madore, Jason, Vilain, Ricardo E., Menzies, Alexander M., Kakavand, Hojabr, Wilmott, James S., Hyman, Jessica, Yearley, Jennifer H., Kefford, Richard F., Thompson, John F., Long, Georgina V., Hersey, Peter, Scolyer, Richard A.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.05.2015; Wiley Subscription Services, Inc
• Subjects: B7-H1 Antigen - metabolism; biomarker; Clinical Trials as Topic; diagnosis; Female; Genetic Heterogeneity; Heterogeneity; Humans; Immunohistochemistry; Immunotherapy; Lymphocytes, Tumor-Infiltrating - immunology; Male; Medical research; Melanoma; Melanoma - immunology; Melanoma - metabolism; Melanoma - pathology; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; pathology; PD-1; PD-L1; Prognosis; Skin Neoplasms - immunology; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Survival Analysis; Tumors; pathology; metastasis; immunotherapy; PD-L1; diagnosis; melanoma; biomarker; PD-1; prognosis; heterogeneity
• ISSN: 1755-1471; 1755-148X; 1755-148X
• DOI: 10.1111/pcmr.12340

Summary 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.