title: Survival of Lung Adenocarcinoma Patients Predicted from Expression of PD-L1, Galectin-9, and XAGE1 (GAGED2a) on Tumor Cells and Tumor-Infiltrating T Cells.
abstract: The immune status of tumors varies, and this may affect the overall survival (OS) of patients. We examined tumors from 120 patients with lung adenocarcinomas with a tissue microarray for T-cell infiltration and the expression of PD-L1 and Galectin-9 (both ligands for inhibitory receptors on T cells), and cancer/testis (CT) antigen XAGE1 (GAGED2a; a tumor antigen often found on lung tumors) expression, to determine their relevance to OS. Patients defined as pStage I-IIIA could be grouped, based on the expression profiles of PD-L1, Galectin-9, and XAGE1, into cluster A, who had prolonged survival, and cluster B, who had shorter survival. The difference in survival of the clusters was confirmed separately for pStage I and pStage II-IIIA patients. Cluster A patients who also had CD4 and CD8 T-cell infiltration showed even better survival, as expected. The findings were confirmed by examining an independent validation cohort of 68 pStage I lung adenocarcinoma patients. Our data showed that PD-L1 expression was a positive indicator, whereas Galectin-9 and XAGE1 expression was negative. In vitro analyses suggested that PD-L1 expression was upregulated by IFNγ secreted from activated T cells in the tumor and Galectin-9 expression was counteracting those T cells. Thus, use of these immune markers enables the creation of a discriminant function with which to classify tumors and predict survival. Cancer Immunol Res; 4(12); 1049-60. ©2016 AACR.
authors: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors: Yoshihiro
authors: Y
authors: Ohue
authors: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors: Koji
authors: K
authors: Kurose
authors: Faculty of Health and Welfare Services Administration, Kawasaki University of Medical Welfare, Okayama, Japan.
authors: Ryohei
authors: R
authors: Nozawa
authors: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors: Midori
authors: M
authors: Isobe
authors: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors: Yumi
authors: Y
authors: Nishio
authors: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Tomonori
authors: T
authors: Tanaka
authors: Department of General Thoracic and Cardiovascular Surgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Yoshinori
authors: Y
authors: Doki
authors: Laboratory of Pathology, Toyama University Hospital, Toyama, Japan.
authors: Takashi
authors: T
authors: Hori
authors: Department of Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Junya
authors: J
authors: Fukuoka
authors: Department of Respiratory Medicine, Kawasaki Medical School, Okayama, Japan.
authors: Mikio
authors: M
authors: Oka
authors: Faculty of Health and Welfare, Kawasaki University of Medical Welfare, Okayama, Japan. nakayamae@okayama-u.ac.jp.
authors: Eiichi
authors: E
authors: Nakayama
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D000077716:Afatinib; D000951:Antigens, Neoplasm / Q000378:metabolism*; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D016019:Survival Analysis
chemical_list: D000077716:Afatinib; D000951:Antigens, Neoplasm; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D037161:Galectins; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C423236:CD274 protein, human; C105032:LGALS9 protein, human; C413656:XAGE1A protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human