Abstract 2700: Effects of anticancer drugs on the viability and the function of peripheral blood mononuclear cells

Abstract

Abstract [Background/Purpose] Cytotoxic chemotherapy is generally considered immunesuppressive because of its toxicity for dividing cells in the bone marrow. However, recent experimental studies support the notion that certain cytotoxic anticancer agents may actually exhibit immune modulatory activities. Effects of anticancer drugs on adoptive transferred cells remain unclear. Therefore, the purpose of this study was to evaluate the effects of anticancer drugs on the viability and the function of peripheral blood mononuclear cells (PBMCs). [Method] 5-FU, CPT-11, CDDP and GEM were assessed in the present experiment. PBMCs were treated with each drug for 2hrs, and then cell viability was determined by trypan blue staining and WST-8 assay. For assessment of effects of each drug on proliferation and cytokine producing ability of PBMCs, PBMCs were stimulated with PHA for 48 hrs, following the treatment with each anticancer drug for 2hrs. Proliferation potency of PBMCs was measured using BrdU cell proliferation assay and the producing ability of various cytokines from PBMCs was measured using ELISA. The percentages of IFN-γ-expressing cells and regulatory T cells (Tregs) in GEM-treated PBMCs were measured using flow cytometric assay. [Results] The anticancer drugs did not affect the cell viability of PBMCs. While 5FU and CPT-11 did not influence proliferation potency, CDDP and GEM inhibited it in concentration-dependent manner. Treatment with GEM enhanced the production of IFN-γ from PBMCs and decreased the number of Tregs induced by PHA. Flow cytometric assay revealed that GEM treatment increased the number of IFN-γ-producing cells in CD4 cells, but GEM did not affect in CD8 cells. [Conclusions] The anticancer drugs did not affect the cell viability of PBMCs in the present experiment. We have found that GEM may be a practical strategy for the enhancement of IFN-γ production from CD4 cells and reduction of Tregs. Thus, GEM should be evaluated in conjunction with a variety of immunotherapy approaches. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2700. doi:10.1158/1538-7445.AM2011-2700