The article details an investigation into the Tumor Microenvironment (TME) of metastatic esophageal squamous cell carcinoma (ESCC). The core finding identifies a distinct subpopulation of pericytes, known as GPR116$^+$ pericytes, which are significantly enriched in metastatic tumors and correlated with a poorer prognosis. Using advanced multi-omics techniques, the study uncovers a mechanism where these pericytes promote metastasis by secreting EGFL6, which then interacts with integrin $eta$1 on cancer cells to activate the NF-$\kappa$B pathway and induce epithelial-mesenchymal transition (EMT). Furthermore, the research demonstrates that targeting this EGFL6–integrin $eta$1–NF-$\kappa$B axis with an inhibitor can significantly suppress metastasis and enhance the efficacy of anti-PD-1 immunotherapy in mouse models. Finally, the authors propose that serum EGFL6 could serve as an effective, noninvasive diagnostic and prognostic biomarker for ESCC and potentially other cancers.
References:
- Pei X, Liu Z, Tang L, et al. Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116+ pericytes in cancer metastasis[J]. Nature Genetics, 2025, 57(10): 2494-2508.
