Obesity and gastrointestinal cancer: the interrelationship of adipose and tumour microenvironments

Increasing recognition of an association between obesity and many cancer types exists, but how the myriad of local and systemic effects of obesity affect key cellular and non-cellular processes within the tumour microenvironment (TME) relevant to carcinogenesis, tumour progression and response to therapies remains poorly understood. The TME is a complex cellular environment in which the tumour exists along with blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, signalling molecules and the extracellular matrix. Obesity, in particular visceral obesity, might fuel the dysregulation of key pathways relevant to both the adipose microenvironment and the TME, which interact to promote carcinogenesis in at-risk epithelium. The tumour-promoting effects of obesity can occur at the local level as well as systemically via circulating inflammatory, growth factor and metabolic mediators associated with adipose tissue inflammation, as well as paracrine and autocrine effects. This Review explores key pathways linking visceral obesity and gastrointestinal cancer, including inflammation, hypoxia, altered stromal and immune cell function, energy metabolism and angiogenesis.