Abstract 2336: Extra-virgin olive oil prevented tumor immune escape and intratumoral metabolic reprogramming in a mouse model of colorectal cancer via promoting T-cell infiltration, DNA repair, attenuation of overexpression of immune checkpoint proteins, glutamine dependency, and the Warburg metabolic phenotype
Authors: Ajayi Babajide O. , Adeshina Anuoluwapo 
Published: April 2023

Abstract
Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. Tumor Immune escape via activation of immune checkpoint proteins, T-cell exhaustion, impaired DNA repair mechanism, and metabolic reprogramming are crucial for CRC initiation, promotion, and progression. Immune checkpoint proteins such as programmed cell death 1 (PD1), PD1 ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA4) act as inhibitory immunoreceptors that prevent cytotoxic T-cells from infiltrating tumor cells. Also, metabolic pathways are actively reprogrammed during CRC development. Indeed, upregulation of DNA repair mechanisms, enhancement of tumor immunosurveillance via immune checkpoint blockage, and inhibition of intratumoral metabolic reprogramming (IMR) can revolutionize CRC treatment and improve patients’ survival. Epidemiological studies have reported the association between the intake of extra virgin olive oil (EVOO) and a reduced risk of CRC development. However, there is a lack of information on the effect of EVOO on DNA repair, tumor immunosurveillance, and IMR in CRC. Therefore, we investigated the effect of EVOO on DNA repair, tumor immunosurveillance, and IMR in mice model of CRC. Male BALB/c mice were divided into five groups of 10 mice each. Group 1 mice served as controls. Group 2 mice received a single dose of azoxymethane (AOM) 10mg/kg and, after one week, they received three cycles of dextran sulfate sodium (DSS) at 3% in their drinking water. Group 3 mice received EVOO (2ml/Kg) by oral gavage in combination with AOM and three cycles of 3% DSS (W/V) in drinking water. Group 4 received EVOO (2ml/Kg) only while Group 5 received 5-fluorouracil (10mg/kg) in combination with AOM and three cycles of 3% DSS (W/V) in drinking water. The experiment was terminated after confirmation of colorectal adenocarcinoma. A high tumor burden was observed to be decreased in CRC mice treated with EVOO. Furthermore, CRC mice treated with EVOO had increased expression of MSH6, PMS2, MLH1, MSH2, P53, CD4+, and CD8+ T-cells and decreased expression of PD1, PD-L1, and CTLA4 when compared to mice with CRC. Also, it decreases the colonic expression of glucose transporters 1 & 4, hypoxia-inducible factor-1 α, pyruvate kinase M2, hexokinase 1 and 2, lactate dehydrogenase, monocarboxylate transporter 4, fatty acid synthase, and glutaminase 1 in CRC mice when compared to the control group. The results obtained from this study showed that EVOO prevented tumor immune escape and IMR in a mouse model of colorectal cancer via promoting T-cell infiltration, DNA repair, and attenuation of overexpression of immune checkpoint proteins, glutamine dependency and Warburg metabolic phenotype.
Citation Format: Babajide O. Ajayi, Anuoluwapo Adeshina. Extra-virgin olive oil prevented tumor immune escape and intratumoral metabolic reprogramming in a mouse model of colorectal cancer via promoting T-cell infiltration, DNA repair, attenuation of overexpression of immune checkpoint proteins, glutamine dependency, and the Warburg metabolic phenotype [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 2336.