Abstract 495: Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance.

Abstract

Abstract BACKGROUND:XAGE-1bis a cancer/testis (CT) antigen expressed highly in non-small cell lung cancer (NSCLC) with restricted expressiononly in testis in normal tissues. In this study, we investigated correlation of intensity of humoral and cellular immune responses against XAGE-1b and itsclinical relevance in NSCLC patients. MATERIALS AND METHODS:Peripheral bloodwas obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2005 and 2012 under written informed consent. Antibody response to XAGE-1bwas analyzed by ELISA using synthesized XAGE-1b protein. CD4 and CD8 T-cell responses were examined by IFN-γ ELISA and/or IFN-γcapture assay by FACS using 12-mer or 16-merXAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b (GAGED2a) protein. RESULTS: Antibody positive frequencies of total 362 NSCLC, 220 lung adenocarcinoma and 85 lung squamous cell carcinoma patients were 8.8% (32/362), 12.7% (28/220) and 1.2% (1/85), respectively. With antibody positive NSCLC patients, the patients showing high, intermediate and low antibody response was 7, 20 and 5, respectively. The frequency of XAGE-1b-reactive CD4 T-cells in patients showing high, intermediate and low antibody response was 5.5 ±2.1 x 10−5, 1.5 ±0.7 x 10−5 and < 1.1 x 10−5, respectively. The frequency of XAGE-1b-reactive CD8 T-cells was 6.9 ±1.6 x 10−6, 4.6 ±1.6 x 10−6 and < 1.1 x 10−6, respectively. The frequency of cytotoxic CD8 T-cells in IFN-γ secreting CD8 T-cells in response to XAGE-1b-peptide-pulsed autologous EBV-B cells in patients showing high and intermediate antibody responses was 59.0% and 4.8%, respectively.We evaluated overall survival (OS) time with 120 stage IIIB/IV lung adenocarcinoma patients. Median OS were 32.3 and 14.4 months in antibody-positive and negative patients(P-.039). There was no significant differencewith 1-year survival rate in antibody-positive (68.7%) and negative (55.6%)patients, but was significant with 3-year survival rate in 34.8% and 14.1% respectively. Furthermore, univariate and multivariable analyses showed XAGE-1b antibody response was independent prognostic factor. CONCLUSION:Our findings indicate that CT antigen XAGE-1b is highly immunogenic in NSCLC patients inducing antibody, and CD4 and CD8 T-cell responses and the immune response against XAGE-1b is beneficial for prognosis. Citation Format: Yoshihiro Ohue, Koji Kurose, Shingo Eikawa, Yu Mizote, Hirofumi Matsumoto, Midori Isobe, Akiko Uenaka, Minoru Fukuda, Eiichi Nakayama, Mikio Oka. Immune response to XAGE-1b (GAGED2a) in NSCLC patients and its clinical relevance. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 495. doi:10.1158/1538-7445.AM2013-495