Tumor fibroblast-derived FGF2 regulates SPRY1 expression in esophageal tumor-infiltrating T cells and plays a role in T cell exhaustion

Using single-cell RNA sequencing, we found that exhausted T cells in esophageal cancer were more heterogeneous than previously clarified. We discovered that SPRY1 was notably enriched in two subsets of exhausted CD8+ T cells. When overexpressed, SPRY1 impaired T cell activation by interacting with CBL, which is a negative regulator of ZAP-70 tyrosine phosphorylation. In this study, we provided a landscape of esophageal tumor-infiltrating T cells using 10x scRNA-seq. We identified a novel exhausted T cell marker gene-SPRY1, which especially upregulated in two subsets of exhausted T cells. We then investigated the biological effect of SPRY1 on TCR signaling and the potential inducement of its upregulation.