Peritumoural adipose tissue drives immune evasion in colorectal cancer via adipose–mesenchymal transformation

Although peritumoural visceral adipose tissue (tVAT) is anatomically close to tumours such as colorectal cancer, the immune landscape of this tissue and its functional contribution to tumour immunity remain poorly defined. Here, we performed single-cell RNA analysis on the tVAT from patients with colorectal cancer to map its immune landscape and observed that tVAT exhibited a highly immune-infiltrated microenvironment enriched with lymphocytes, especially tumour-specific CD8⁺ T cells. Mechanistically, tVAT competes with the tumour for these immunocytes by activating the CXCL12–CXCR4 axis to promote tumour immune escape. Moreover, tumour-derived factors induce an adipose–mesenchymal transformation process where the adipose stromal cells trans-differentiated into adipose-derived cancer-associated fibroblasts, which secrete large amounts of CXCL12 in tVAT. Clinically, targeting adipose–tumour interaction substantially enhances diagnostic and therapeutic efficacy of anti-PD-1 therapy. These findings offer an understanding of the dynamic crosstalk between tVAT and tumour immune escape, highlighting the tVAT as a potential target for cancer immunotherapy. Wang, Zheng, Qian, Pan, Tian et al. characterize the crosstalk between peritumoural visceral adipose tissue and colorectal tumour microenvironment and report an immune escape mechanism, which may be potentially targeted for improved immunotherapy.