Figure S1 - OS of lung adenocarcinoma patients with TILs. Figure S2 - Discriminant scores of each lung adenocarcinoma patient calculated by the discriminant function. Figure S3 - OS of lung adenocarcinoma patients belonging to predicted clusters with the study cohort and validation cohort. Figure S4 - Correlation of PD-L1 and Galectin-9 expression and T-cell infiltration in the tumor - Figure S5 - RT-PCR analysis of XAGE1 mRNA. Figure S6 - Effect of IFNgamma on PD-L1 and Galectin-9 expression in cell lines.
Funding
Ministry of Health, Labour and Welfare, Japan
JSPS KAKENHI
Takeda Science Foundation
Medical Research Encouragement Prize of The Japan Medical Association
Kawasaki Medical School and Kawasaki University of Medical Welfare
ARTICLE 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.
