Abstract 6798: CD8α+ dendritic cells potentiate the antitumor and immune activities against murine ovarian cancers

Abstract

Abstract Objectives: Dendritic cell (DC) based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. This study aimed to evaluate the effectiveness of mouse CD8α+ dendritic cells (DCs), corresponding to human CD141+ DCs, derived from bone marrow (BM) hematopoietic stem cells (HSCs) in a syngeneic and orthotopic mouse ovarian cancer model. Methods: Stem-DCs from HSCs and Mono-DCs from monocytes were generated from the bone marrow mononuclear cells (BM-MNCs) of C57BL/6 mice in condition of pulsing with ID8 tumor cell lysates. C57BL/6 mice were intraperitoneally injected with 5 × 106 ID8 cells. They were treated with vehicle, low/medium/high dose pulsed Stem-DCs, Mono-DCs, and unpulsed Stem-DCs. At 8 to 9 weeks, the treated mice were sacrificed, and tumor responses and immune responses, such as lymphocyte proliferation and cytokine secretion, were analyzed. Results: Mono-DCs and Stem-DCs were characterized by CD11c+CD80+CD86+ and CD8α+Clec9a+ expression, respectively. They were confirmed by the secretion of immunostimulatory cytokines, such as interleukin (IL)-12 and interferon (IFN)-γ, and T cell proliferation was observed after maturation. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle treated mice (P = 0.0021 and P = 0.0092, respectively). These mice treated with pulsed Stem-DCs appeared to have fewer tumor implants which were usually confined in the epithelium of ovaries, diaphragm and peritoneum. All mice injected with DCs demonstrated longer survival than the vehicle group (P = 0.0187), especially the medium/high dose pulsed Stem-DC treatment groups. Moreover, these favorable tumor responses were associated with a low proportion of myeloid-derived suppressor cells (MDSCs) and regulatory T cells, high IL-12 and IFN-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Conclusions: We demonstrated that mouse CD8α+ DCs derived from BM HSCs could decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs. Citation Format: Shin-Wha Lee, Dasol Oh, Hyunah Lee, Kyung-Won Lee, Min-Je Kim, Sung Wan Kang, Young-Jae Lee, HyunSoo Kim, Yong-Man Kim. CD8α+ dendritic cells potentiate the antitumor and immune activities against murine ovarian cancers. [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 6798.