Yuki Katsuya1, Yu Fujita2, Hidehito Horinouchi3, Yuichiro Ohe3, Shun-Ichi Watanabe4, Koji Tsuta5. 1. Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 2. Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan. 3. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 4. Division of Thoracic Surgery, National Cancer Center Hospital, Tokyo, Japan. 5. Division of Pathology and Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan. Electronic address: ktsuta@ncc.go.jp.
Abstract
PURPOSE: The immune checkpoint ligand programmed cell death 1 ligand 1 (PD-L1) is expressed in various tumors and is associated with the response to anti programmed cell death 1 (PD-1)/PD-L1 drugs. We evaluated PD-L1 expression in thymomas and thymic carcinomas to determine whether PD-L1 represents a therapeutic target in unresectable thymomas or thymic carcinomas that could be amenable to antibody-based immunotherapy. METHOD: A tissue microarray (TMA) comprised of 101 thymomas and 38 thymic carcinomas samples was evaluated. After validation of the rabbit monoclonal PD-L1 antibody (clone E1L3N), the TMA was stained and the tumor PD-L1 expression score was calculated using a semiquantitive method (by multiplying the intensity [0-3] by the staining area [0-100%]). RESULTS: Seventy percent of thymic carcinoma (type C) and 23% of thymoma (types A, AB, and B) samples stained positive for PD-L1 (P<.001). A WHO classification (type C vs types A, AB, and B) was significantly associated with positive PD-L1 expression (P=0.006), though multivariate analysis did not show PD-L1 positive was a significant negative factor of overall survival (hazard ratio=0.99, 95% confidence interval=0.35-2.73; P=0.987). CONCLUSIONS: To the best of our knowledge, this is the largest-scale study to evaluate PD-L1 expression in thymomas and thymic carcinomas. The data suggest that the anti PD-1/PD-L1 drug could be of potential use in immunotherapy for unresectable or relapsed thymomas and thymic carcinomas.
PURPOSE: The immune checkpoint ligand programmed cell death 1 ligand 1 (PD-L1) is expressed in various tumors and is associated with the response to anti programmed cell death 1 (PD-1)/PD-L1 drugs. We evaluated PD-L1 expression in thymomas and thymic carcinomas to determine whether PD-L1 represents a therapeutic target in unresectable thymomas or thymic carcinomas that could be amenable to antibody-based immunotherapy. METHOD: A tissue microarray (TMA) comprised of 101 thymomas and 38 thymic carcinomas samples was evaluated. After validation of the rabbit monoclonal PD-L1 antibody (clone E1L3N), the TMA was stained and the tumorPD-L1 expression score was calculated using a semiquantitive method (by multiplying the intensity [0-3] by the staining area [0-100%]). RESULTS: Seventy percent of thymic carcinoma (type C) and 23% of thymoma (types A, AB, and B) samples stained positive for PD-L1 (P<.001). A WHO classification (type C vs types A, AB, and B) was significantly associated with positive PD-L1 expression (P=0.006), though multivariate analysis did not show PD-L1 positive was a significant negative factor of overall survival (hazard ratio=0.99, 95% confidence interval=0.35-2.73; P=0.987). CONCLUSIONS: To the best of our knowledge, this is the largest-scale study to evaluate PD-L1 expression in thymomas and thymic carcinomas. The data suggest that the anti PD-1/PD-L1 drug could be of potential use in immunotherapy for unresectable or relapsed thymomas and thymic carcinomas.
Authors: Hyun-Sung Lee; Hee-Jin Jang; Rohan Shah; David Yoon; Masatsugu Hamaji; Ori Wald; Ju-Seog Lee; David J Sugarbaker; Bryan M Burt Journal: Clin Cancer Res Date: 2017-04-11 Impact factor: 12.531
Authors: Dwight Owen; Benjamin Chu; Amy M Lehman; Lakshmanan Annamalai; Jennifer H Yearley; Konstantin Shilo; Gregory A Otterson Journal: J Thorac Oncol Date: 2018-04-24 Impact factor: 15.609