Abstract 4218: 6-gingerol upregulated CD8+ T cells function in mice model of colorectal cancer via modulation of programmed cell death protein 1/programmed death-ligand1 and cytotoxic T-lymphocyte-associated protein 4 receptor signaling

Abstract

Abstract Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States, with about 149,500 new cases of CRC diagnosed in 2021. Although various treatments are available for CRC, survival rates of CRC patients remain very poor. In the last few decades, Inhibition of immune checkpoint proteins have been shown to be a promising strategy for CRC treatments, thus allowing T cells to destroy CRC cells. 6-gingerol, an active compound present in fresh ginger have been shown to possess anti-cancer and immunomodulatory properties. We have previously described the anti-metastatic effect 6-gingerol in CRC. However, there is paucity of information on the effect 6-gingerol on CD8+ T cell function and immune checkpoints proteins in CRC. Therefore, this study investigated the effect of 6-gingerol on CD8+ T cells function and immune check point proteins in using mice model of CRC and system biology approach. Male BALB/c mice were divided into four groups of 10 mice each. Group 1 mice serve as control, group 2 mice received 6-gingerol 10mg/kg/day by oral gavage for 10 weeks. Group 3 (CRC model) mice received a single dose of azoxymethane 10mg/kg (Intraperitoneal) and on the seventh day they received three cycles of dextran sulfate sodium (DSS) 2% (W/V) in drinking water (each cycle is defined as one week of 2% DSS followed by two weeks of plain drinking water) Group 4 mice received 6-gingerol 10mg/kg/day by oral gavage in combination with single dose of azoxymethane 10mg/kg (iP) and three cycles of 2% DSS (W/V) in drinking water. Administration of 6-gingerol to AOM/DSS treated mice increase the percentage (%) gated cells population of CD8+Tcells and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) with concomitant decrease in % gated population of Programmed cell death protein 1 (PD-1) and B-7 proteins as compared to AOM/DSS only treated mice. Furthermore, there was decrease expression of PD-L1 on colon tissues of 6-gingerol treated mice when compared with AOM/DSS treated mice colon. Also, using system biology analysis, we observed a high binding energy of 6-gingerol with PD-1/PD-L1 Complex, PD-L1, Dimeric PD-L1 and CTLA-4/B7-2 complex proteins. The result obtained from this study showed that 6-gingerol inhibited immune check point proteins and upregulated CD8+ T cells function in colorectal cancer via modulation of PD-1/PD-L1 and CTLA4 receptor signaling, and as such 6-gingerol could be a promising natural product for CRC immunotherapy. Citation Format: Babajide O. Ajayi, Anuoluwapo Adeshina. 6-gingerol upregulated CD8+ T cells function in mice model of colorectal cancer via modulation of programmed cell death protein 1/programmed death-ligand1 and cytotoxic T-lymphocyte-associated protein 4 receptor signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4218.