title: PD-L1 expression in melanoma shows marked heterogeneity within and between patients: implications for anti-PD-1/PD-L1 clinical trials.
abstract: 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.
authors.affiliation: Melanoma Institute Australia, Sydney, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
authors.forename: Jason
authors.initials: J
authors.lastname: Madore
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Vilain
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Menzies
authors.forename: Hojabr
authors.initials: H
authors.lastname: Kakavand
authors.forename: James S
authors.initials: JS
authors.lastname: Wilmott
authors.forename: Jessica
authors.initials: J
authors.lastname: Hyman
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Yearley
authors.forename: Richard F
authors.initials: RF
authors.lastname: Kefford
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
authors.forename: Georgina V
authors.initials: GV
authors.lastname: Long
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
authors.forename: Richard A
authors.initials: RA
authors.lastname: Scolyer
mesh_terms: D060890:B7-H1 Antigen / Q000378:metabolism*; D002986:Clinical Trials as Topic; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011379:Prognosis; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D060890:B7-H1 Antigen
keywords: PD-1; PD-L1; biomarker; diagnosis; heterogeneity; immunotherapy; melanoma; metastasis; pathology; prognosis