Purpose: XAGE1 is a cancer/testis antigen and expressed in ~40% of advanced lung adenocarcinomas. Antibody response to XAGE1 was frequently observed in those patients. Furthermore, CD4 and CD8 T-cell responses against XAGE1 could be frequently detected in antibody positive patients. The overall survival (OS) of XAGE1 antibody-positive patients was prolonged significantly compared to the antibody-negative patients. Thus the XAGE1 immune response appeared to be involved in the patient prognosis. In this study, we studied other immune regulation mechanisms than XAGE1 immunity in lung adenocarcinoma patients. We found positive and negative involvement of PD-L1 and Gal-9, respectively, for patient prognosis. Based on the findings, we developed a discriminant function capable of efficiently predicting the patient prognosis using those immune parameters.
Experimental Design: XAGE1, PD-L1 and Gal-9 expression in lung cancer was investigated using tissue microarray (TMA) including 194 adenocarcinomas, 112 squamous cell carcinomas, 17 small cell carcinomas, and 11 others, and 32 metastatic lung tumors by IHC. Tumor infiltrating lymphocytes were analyzed by automated scan scope. Clinical relevance of XAGE1, PD-L1, Gal-9 expression on tumor cells, and tumor infiltrating lymphocytes was evaluated in lung adenocarcinoma patients.
Results: Frequency of PD-L1, Galectin-9 and XAGE1 expression on lung adenocarcinoma was 49.0%, 31.4% and 27.8%, respectively. OS of the patients with high PD-L1 expressing tumors was prolonged compared to the patients with low/- expressing tumors. On the other hand, OS of the patients with high Galectin-9 or XAGE1 expressing tumors was shortened compared to the patients with low/- expressing tumors. OS of the patients with high T cell infiltration in the tumor was prolonged compared to the patients with low/- T cell infiltration. By using the parameters including PD-L1, Gal-9 and XAGE1 expression on tumor cells, and CD4 and CD8 T-cell infiltration score in the tumor, we developed a discriminant function capable of efficiently predicting overall survival in lung adenocarcinoma patients
Conclusions: OS of the lung adenocarcinoma patient was clearly predictable using the discriminant function developed using the immune parameters including PD-L1, Gal-9 and XAGE1 expression on tumor cells, and CD4 and CD8 T-cell infiltration score in the tumor independently from TNM classification. The findings suggested the involvement of PD-1/PD-L and Tim-3/ Gal-9 pathways of immune regulation, and of XAGE1 immune response, in the tumor microenvironment for prognosis of the lung adenocarcinoma patients. Those parameters are useful as biomarkers.
Citation Format: Yoshihiro Ohue, Kurose Koji, Mikio OKa, Eiichi Nakayama. Discriminant function for predicting survival of lung adenocarcinoma patients developed by using immune parameters of PD-L1, Gal-9, and XAGE1 expression on tumor cells and T cell infiltration score. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A008.
- ©2016 American Association for Cancer Research.