OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. RESULTS: Compared with PD-L1 negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08-2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05-2.67; P = 0.033]. TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001) and high CD8 expression (P < 0.0001). A stratification based on PD-L1 expression and TIL status was also significantly associated with overall survival (log rank P < 0.0001). CONCLUSIONS: PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.
OBJECTIVES: To examine the prognostic impact of the programmed death ligand 1 (PD-L1) expression, tumor-infiltrating lymphocyte (TIL) status, and their combination in esophageal cancer. SUMMARY BACKGROUND DATA: PD-L1 has garnered much attention for its roles in tumor immunology and as an immune-based therapeutic target. To ensure a response to PD-L1 checkpoint inhibitor, a new framework based on PD-L1 expression and the presence or absence of TILs is required. METHODS: Using a nonbiased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (cluster of differentiation 8 (CD8) expression) by immunohistochemical analysis. The Cox proportional hazard model was used to compute the hazard ratio (HR) for mortality. RESULTS: Compared with PD-L1 negative cases (n=252), PD-L1 positive cases (n = 53) showed significantly worse overall survival [log-rank P = 0.016; HR: 1.71; 95% confidence interval: 1.08-2.61; P = 0.024; multivariate HR: 1.69; 95% confidence interval: 1.05-2.67; P = 0.033]. TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001) and high CD8 expression (P < 0.0001). A stratification based on PD-L1 expression and TIL status was also significantly associated with overall survival (log rank P < 0.0001). CONCLUSIONS:PD-L1 expression was associated with an unfavorable clinical outcome in esophageal cancer, supporting its role as a prognostic biomarker. In addition, the combination with TIL status enabled further classification patients according to clinical outcome. PD-L1 expression and TIL status may serve as predictive tissue biomarkers and can be used for patient selection in clinical trials of drugs targeting the PD-1/PD-L1 pathways.
Authors: Tsuyoshi Hamada; Thing Rinda Soong; Yohei Masugi; Keisuke Kosumi; Jonathan A Nowak; Annacarolina da Silva; Xinmeng Jasmine Mu; Tyler S Twombly; Hideo Koh; Juhong Yang; Mingyang Song; Li Liu; Mancang Gu; Yan Shi; Katsuhiko Nosho; Teppei Morikawa; Kentaro Inamura; Sachet A Shukla; Catherine J Wu; Levi A Garraway; Xuehong Zhang; Kana Wu; Jeffrey A Meyerhardt; Andrew T Chan; Jonathan N Glickman; Scott J Rodig; Gordon J Freeman; Charles S Fuchs; Reiko Nishihara; Marios Giannakis; Shuji Ogino Journal: Oncoimmunology Date: 2018-03-19 Impact factor: 8.110
Authors: Ramy R Saleh; Jordan L Scott; Nicholas Meti; Danielle Perlon; Rouhi Fazelzad; Alberto Ocana; Eitan Amir Journal: Mol Diagn Ther Date: 2022-02-01 Impact factor: 4.074