Adipose tissue from oesophageal adenocarcinoma patients is differentially affected by chemotherapy and chemoradiotherapy regimens altering immune cell phenotype and cancer cell metabolism

Oesophageal adenocarcinoma (OAC) is a poor prognosis cancer with limited responses to standard of care treatments including chemotherapy and chemoradiotherapy. OAC has one of the strongest associations with obesity, its anatomical location surrounded by visceral adipose tissue has been postulated to intensify this association. Adipose tissue is a regulatory organ with many unknown downstream functions, including its direct response to chemotherapy and radiotherapy. To elucidate the role of visceral adipose tissue in this disease state, metabolic and secreted pro-inflammatory cytokines analysis was conducted on human ex-vivo adipose tissue explants following exposure to FLOT-chemotherapy and CROSS-chemoradiotherapy. To assess how these complex treated microenvironments impact cancer cell metabolism, dendritic cell, and macrophage phenotype, mitochondrial bioenergetics and surface markers expression were examined using seahorse technology and flow cytometry respectively. This study observed that chemotherapy and chemoradiotherapy differentially alter adipose tissue metabolism and secretome, with chemoradiotherapy increasing pro-inflammatory associated mediators (p