Abstract 508: Correlation of antibody and T-cell responses against XAGE-1b in NSCLC patients

BACKGROUND: XAGE-1b is a cancer/testis antigen identified in lung cancer using autologous patient serum by SEREX. The expression of XAGE-1b is observed frequently in lung adenocarcinoma and rarely in some other tumors. Recently, we showed spontaneous T-cell response against XAGE-1b in XAGE-1b-antibody positive non-small cell lung cancer (NSCLC) patients. In this study, we analyzed the frequency of XAGE-1b-reactive CD4 and CD8 T-cells in NSCLC patients showing high, intermediate and low antibody responses. MATERIALS AND METHODS: Sera and PBMCs were obtained from NSCLC patients who visited Kawasaki Medical School Hospital between 2009 and 2011. Antibody response was determined for XAGE-1b protein by ELISA using O.D. values at 1:900 serum dilution and classified as high ≥ 3.0, 3.0 > intermediate ≥ 1.0 and 1.0 > low. CD4 and CD8 T-cell responses against XAGE-1b were examined by IFN-γ ELISA using 12- or 16-mer XAGE-1b-overlapping peptides (OLPs) spanning the entire XAGE-1b protein in antibody-positive patients. Cytotoxicity was analyzed determining GAPDH release by aCellaTox kit. RESULTS: The number of XAGE-1b-antibody positives was 29 (9.0%) of 323 NSCLC patients. Within those, the patients showing high, intermediate and low antibody response was 6, 11 and 12, 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 ratio of the CD8 T-cells recognizing XAGE-1b-expressing tumor to the XAGE-1b-peptide reactive CD8 T-cells in patients showing high and intermediate antibody responses was 60.0% and 14.3%, respectively. CONCLUSION: Our findings indicate correlation of antibody response to CD4 and CD8 T-cell responses against XAGE-1b in NSCLC patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 508. doi:1538-7445.AM2012-508