Abstract 6351: Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature

Abstract Clinical trials on cholangiocarcinoma revealed differential sensitivity to cytolytic action of allogeneic cytokine-induced killer (CIK) cells. Different metastatic foci in the same individual could also display different sensitivity. The differential sensitivity of separate lines of cultured cholangiocarcinoma cells could be demonstrated based on the evaluation of GR50. Allogeneic CIK cell or CD3+CD56+ subset was co-cultured with nine cell lines at E:T ratio of 20:1 for 48 h. The tumor cells were categorized into 2 groups based on the obtained GR50. This resulted in 4 sensitive cell lines and 5 resistant cell lines. The cholangiocarcinoma cell-exposed CIK cell and CD3+CD56+ subset displayed defective anti-tumor cytotoxicity upon subsequent experiment. RNAseq analysis revealed 261 genes upregulated in sensitive cell lines and 665 genes upregulated in resistant cell lines. The top 50 resistant genes were evaluated for their linked signal transduction and protein interaction network. Based on the interaction network, a list of chemicals that could interrupt the stipulated network were selected. They were assayed for their synergistic activity with dysfunctional CIK cell or CD3+CD56+ subset for cytolysis of resistant tumor cells. Citation Format: Adisak Wongkajornsilp, Khin Su Su Htwe, Porncheera Chusorn, Sunisa Duangsa-ard, Kanda Kasetsinsombat, Nathawadee Sawatpiboon. Reversal of dysfunctional CIK cells after the exposure to resistant cholangiocarcinoma cells through chemical perturbation of resistant gene signature [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6351.