High antigen-presenting CAF levels correlate with reduced glycosaminoglycan biosynthesis-heparan sulfate/heparin metabolism in immune cells and poor prognosis in esophageal squamous cell carcinoma: Insights from bulk and single-cell transcriptome profiling.

Abstract

In esophageal squamous cell carcinoma (ESCC), the tumor microenvironment (TME) is characterized by a significant accumulation of cancer-associated fibroblasts (CAFs), which play a pivotal role in the host response against tumor cells. While fibroblasts are known to be crucial in the metabolic reprogramming of the TME, the specific metabolic alterations induced by these cells remain largely undefined. Utilizing single-cell RNA sequencing, we have identified a distinct subpopulation of antigen-presenting CAF (apCAF) within ESCC tumors. Our findings reveal that apCAF contribute to adverse patient outcomes by remodeling the tumor metabolic environment. Notably, apCAF modulate the glycosaminoglycan biosynthesis-heparan sulfate/heparin metabolism pathway in T cells, B cells, and macrophages. Disruption of this pathway may facilitate immune evasion by the tumor. These insights underscore the critical role of CAFs in shaping the metabolic landscape of the TME and lay the groundwork for developing therapeutic strategies aimed at enhancing anti-tumor immunity.