Abstract 1096: Response of pancreatic ductal adenocarcinoma to gemcitabine using human organotypic slice cultures

Abstract

Abstract Background/Objective: The oragnotypic tumor slice culture model resembles the in vivo situation of tumor. It may serve as a proper ex vivo platform for response to anti-tumor therapies. We aimed to evaluate the response of pancreatic ductal adenocarcinoma (PDA) cells and helper, cytotoxic, and regulatory T cells to gemcitabine using human PDA slice culture model. Methods: PDA tissues were obtained from patients who were operated on for pancreatic resection. The tumors were sliced by a vibratome, and the tumor slices were then cultured until 5 days with 0.1 μM, 1 μM, and 10 μM gemcitabine for 1 or 2 days. Tumor responses were evaluated by number of tumor cells and proportion of Ki-67 or caspase-3 positively expressed cells in the tumor. CD4+, CD8+, and FOXP3+ cells were analyzed by immunohistochemistry staining. Results: Gemcitabine treatment to PDA slices exerted proportional cytotoxic effects in terms of tumor cell number, and Ki-67 and cleaved caspase-3 expression. Mean Ki-67 positive cells in PDA cells tended to decrease according to increase of gemcitabine concentration (case 1, 48 hr treatment; 65.7% in control vs. 27.9% in 0.1 μM, p=0.025). Mean caspase-3 positive cells in PDA cells tended to increase according to increase of gemcitabine concentration (case 1, 48 hr treatment; 8.6% in control vs. 18.6% in 0.1 μM, p=0.042). Mean PDA cells per x200 tended to decrease according to increase of gemcitabine concentration (case 2, 48 hr treatment; 78.3 in 1.0 μM vs. 27.3 in 10 μM, p=0.042). Mean CD4+, CD8+, and FOXP3+ cells/total cells tended to decrease according to increase of gemcitabine concentration; in case 3 (24hr treatment), mean CD4+ cells/total cells decreased as 2.6%, 1.6%, 1.5%, and 0.5%, mean CD8+ cells/total cells decreased as 2.6%, 1.5%, 1.4%, and 1.1%, and mean FOXP3+ cells/total cells were 0.2%, 0.3%, 0.2%, and 0.1% in control, 0.1 μM, 1 μM, and 10 μM gemcitabine, respectively. However, mean CD8+/FOXP3+ cell ratio did not significantly decrease, and even increase from 4.4 in 0.1 μM to 8.6 in 1 μM (p=0.039). Conclusions: Tumoricidal effect of gemcitabine could be demonstrated using organotypic slice culture model. T cells in the tumor decreased according to increase of gemcitabine concentration; however CD8+/FOXP3+ cell ratio relatively maintained. Citation Format: Jae Hyuck Chang, Chae Yoon Lim, Weon Sun Lee, Guk Jin Lee. Response of pancreatic ductal adenocarcinoma to gemcitabine using human organotypic slice cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1096.