Obesity is associated with increased risk and worse prognosis of a range of cancers including colorectal cancer (CRC). A study in Science Immunology shows that increased intratumoral acidity in the context of obesity can increase the pro-tumorigenic activity of tumour-associated macrophages (TAMs) through the acid-sensing receptor GPR65, resulting in accelerated tumour growth.

RNA sequencing (RNA-seq) of TAMs from MC38 tumours showed that TAMs from HFD-fed mice had decreased expression of pro-inflammatory genes and increased expression of genes associated with extracellular matrix, angiogenesis and epithelial–mesenchymal transition compared with TAMs from CD-fed mice. At the protein level, TAMs from HFD-fed mice had decreased secretion of pro-inflammatory cytokines (such as TNF).