Abstract 3452: Investigating the relationship between obesity-related dyslipidemia, inflammatory myeloid cells, and cancer

Abstract Background: Since people with obesity generally have altered immune responses, a high level of cholesterol, and a higher risk for cancer development and progression, it is important to investigate the relationship between cholesterol, immune cells, and cancer. The current study aims to assess the contribution of obesity-related excess lipids in priming subset of myeloid cells. Methods: The carcinogen diethylnitrosamine (DEN) was used to induce hepatocellular carcinoma (HCC) in mice (Wild-type and liver-specific Alb-CPT1-Knockout) and diet-induced obesity (DIO) was induced to evaluate the impact of obesity compared to lean mice. Tumor burden and transcriptomic profiling were performed. In vitro exposure to immature myeloid cells (IMCs) from mice bone marrow with LDL-cholesterol (LDLc) was performed for molecular (protein, RNAseq, ATACseq) assessments and functionality. Results: Obesity induced by diet increased the tumor burden on mice associated with steatosis and accumulation of myeloid-derived suppressor cells in the liver identified by flow cytometry. CPT1-KO mice showed increased gene expression of markers for immunosuppressive neutrophilic subtype and macrophages. Among different pathways, differentially expressed genes were involved in the MET and TGFb Signaling- ECM Remodeling & Metastasis, Inflammation and Epigenetic & Transcriptional Regulation. LDLc in vitro stimulation of IMCs increased the expression of immunosuppressive markers. Integration of RNAseq-ATACseq suggests that lipid-exposed IMCs have an epigenetically regulated activation program. Conclusion: Excess lipids facilitate liver cancer where inflammatory neutrophilic cells and macrophages may play a major contributing role. Funding: Pennington Research Center NORC U54-GM104940 and LSU LCMC Health Cancer Center. Citation Format: Maria D. Sanchez-Pino, Ramesh Thylur Puttalingaiah, Dorota Wyczechowska, Timothy Kayes, Julia Panov, Jone Garai, Timothy Foster, Jovanny Zabaleta. Investigating the relationship between obesity-related dyslipidemia, inflammatory myeloid cells, and cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3452.