title: PD-L1 is an independent prognostic predictor in gastric cancer of Western patients.
abstract: Targeting the PD-1/PD-L1 immune checkpoint signaling is a novel promising treatment strategy in several tumor entities, and it is suggested that PD-L1/PD-1 expression is predictive for a PD-1/PD-L1 checkpoint inhibitor treatment response. We investigated the expression of PD-L1 and PD-1 by immunohistochemistry in a large and well characterized gastric cancer (GC) cohort of Caucasian patients, consisting of 465 GC samples and 15 corresponding liver metastases. Staining results were correlated with clinico-pathological characteristics and survival. PD-L1 expression was found in tumor cells of 140 GCs (30.1%) and 9 liver metastases (60%) respectively in immune cells of 411 GCs (88.4%) and 11 liver metastases (73.3%). PD-1 was expressed in tumor infiltrating lymphocytes in 250 GCs (53.8%) and in 11 liver metastases (73.3%). PD-L1 expression was significantly more prevalent in men, GCs of the proximal stomach, unclassified, papillary, Her2/neu-positive, Epstein-Barr-virus-positive, microsatellite instable, and PIK3CA-mutated GCs. A high PD-L1/PD-1 expression was associated with a significantly better patient outcome, and PD-L1 turned out to be an independent survival prognosticator. The correlation of PD-L1/PD-1 expression with distinct clinico-pathological patient characteristics may serve as a surrogate marker of PD-L1-positive GCs and may direct the use of immune checkpoint treatment strategies.
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Böger
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Behrens
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Micaela
authors.initials: M
authors.lastname: Mathiak
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Krüger
authors.affiliation: Department of Experimental Cancer Research, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.affiliation: Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
mesh_terms: D000368:Aged; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D011379:Prognosis; D013274:Stomach Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D044465:White People
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human
keywords: immune therapy; pembrolizumab; predictive biomarker; programmed death-1