Abstract A42: CD8+PD-1+ cells population were associated with the superiority of DC/CIK cell immunotherapy combined S-1 in patients with advanced pancreatic and gastric cancer

Abstract

Abstract Purpose: Advanced pancreatic(APC) and gastric cancer(AGC) remain challenging to treat effectively. This study aims to investigate the potential role of CD8+PD-1+ T-cells population on the superiority of immunotherapy with dendritic cells and cytokine induced killer cells (DC-CIK) administered with the chemotherapy(S-1). Methods: Consecutive patients with advanced pancreatic cancer (n=36) and gastric cancer (n=30) were treated with either DC-CIK or DC-CIK+S-1. CIK cells were expanded with IL-2. Flow cytometry and ELISPOT were used for sorting and testing the reactivity CD8+PD-1+ T-cells. Survival estimates were calculated according to the Kaplan and Meier methodology. Results: The median overall survival(OS) and progression free survival(PFS) for DC-CIK plus S-1 were 212 and 136 days which were significantly higher than other groups for treatment of APC(P<0.001). Similarly, significant differences in PFS and OS were showed in DC-CIK plus S-1 for treatment of AGC(P<0.001). PD-1- and PD-1+ DC-CIK cells were cocultured with their autologous tumor cell lines, and reactivity was assessed by measuring IFN-γ secretion. We found a clear correlation between the percentage of CD8+PD-1+ T-cells on day 7 of culture and the reactivity of the DC-CIKs after 14 days in culture with IL-2. Moreover, CD8+PD-1+ T-cells showed higher tumor specific IFN-γrelease in ELISPOT, compared to CD8+ PD-1- sorted T-cells or unsorted. Further survival analysis showed that patients with the percentage of CD8+PD-1+ T-cells population enhanced more than 2 times after culture had favorable OS and PFS compared with those having no CD8+PD-1+ T-cells increasing. These results showed that CD8+PD-1+ T-cells population might be an excellent biomarker for tumor or antigen-specific activation of adoptive cell therapy. Conclusion: CD8+PD-1+ T-cells populations were associated with the superiority of DC/CIK combined S-1 and could be a useful biomarker for enriching tumor specific T-cells for cell immunotherapy of patients with APC and AGC. Citation Format: Jun Ren, Guoliang Qiao, Xiaoli Wang, Xinna Zhou, Lefu Huang. CD8+PD-1+ cells population were associated with the superiority of DC/CIK cell immunotherapy combined S-1 in patients with advanced pancreatic and gastric cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr A42.