Adipose tissue and adipocytes have been implicated in promoting tumour progression and hindering anti-tumour immunity. Given that colorectal cancer (CRC) is generally surrounded by abundant visceral adipose tissue (VAT), Wang et al. investigated the functional role of tumour-associated VAT (tVAT) in regulating anti-tumour immunity and immunotherapy efficacy.
Hypothesizing that cytokine-mediated signalling could underlie the variation in immune cell recruitment by adipose tissue, the authors analysed intercellular communication in the scRNA-seq dataset. They found that signatures of CXCL12–CXCR4 signalling, known to regulate T cell trafficking and tissue retention, were markedly elevated in tVAT compared to dVAT or tumour tissue, suggesting this may promote preferential recruitment of cytotoxic CD8+ T cells into the tVAT. Both administration of a CXCL12 neutralizing antibody into the PAT of tumour bearing mice or conditional knockout of Cxcl12 within the PAT of a mouse model of CRC led to smaller tumour growth and increased tumour infiltration of CXCR4+ immune cells, confirming the functional relevance of CXCL12–CXCR4 signalling.
