Däste, SilvioEppenberger-Castori, SerenellaMele, ValentinaSchäfer, Hannah M.Schmid, LukasWeixler, BenjaminSoysal, Savas D.Droeser, Raoul A.Spagnoli, Giulio C.Kettelhack, ChristophOertli, DanielTerracciano, LuigiTornillo, Luigivon Holzen, Urs2020-07-312020-07-312020-04-28Däster, S., Eppenberger-Castori, S., Mele, V., Schäfer, H. M., Schmid, L., Weixler, B., Soysal, S. D., Droeser, R. A., Spagnoli, G. C., Kettelhack, C., Oertli, D., Terracciano, L., Tornillo, L., & von Holzen, U. (2020). Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis. Frontiers in medicine, 7, 144. https://doi.org/10.3389/fmed.2020.00144https://hdl.handle.net/1805/23476Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (rs = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (rs = 0.435, P = 0.0003, and rs = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments.en-USAttribution 4.0 InternationalGastric cancerEsophageal cancePD-1PD-L1CD8+ lymphocyte infiltrationArticle