Abstract 1990: Exploring the immune-metabolic mechanisms of adipose tissue in oesophageal adenocarcinoma

Background: Oesophageal Adenocarcinoma (OAC) is the most strongly associated cancer with obesity. Approximately 75% of OAC patients are obese which results in chronic systemic low-grade inflammation, which is believed to drive carcinogenesis as well as influencing radiation treatment response. Adipose tissue is a regulatory organ with many downstream effects which are still not understood. This study aims to elucidate what influence adipose tissue metabolism and secretome have in treatment resistance and whether obesity alters this response. Methods: Following patient consent, ex-vivo Visceral Adipose Tissue (VAT) explants were exposed to increasing doses of radiation with/without Palmitate and Oleate. Agilent Seahorse Xfe24 was used to measure oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in VAT explants and mitochondrial metabolic parameters in dendritic cells (DCs) following treatment with Adipose Conditioned Media (ACM). Levels of DC maturation following irradiated ACM exposure and Macrophage (Mɸ) polarisation following ACM or Tumour Conditioned Media (TCM) exposure were analyzed by flow cytometry. Irradiated ACM and TCM were analyzed via MSD 54plex ELISA to assess secreted factors on angiogenic, chemokine, cytokine, inflammatory, TH17 or vascular injury panels. Results: VAT explant energy metabolism showed a significant increase for OCR and ECAR with obesity and increasing radiation exposure however OCR was significantly decreased following Palmitate treatment compared with untreated and Oleate treated adipose explants (p