Single-cell RNA sequencing reveals an IL1R2+Treg subset driving immunosuppressive microenvironment in HNSCC

Regulatory T cells (Tregs) play an immunosuppressive role in tumor microenvironment (TME) in various of cancer types. However, how different Treg subsets influence and effect on head and neck squamous cell carcinoma (HNSCC) remain unclear. Here, using single-cell RNA sequencing (scRNA-seq), we identified an IL1R2+Treg subset which promoted the progression of HNSCC. Via tissue microassay (TMA) and enzyme-linked immunosorbent assay (ELISA), we verified the clinical diagnostic value of the IL1R2+Treg and soluble IL1R2 (sIL1R2). In addition, we constructed tumor-bearing mouse models to explore the antitumor effects of combined targeting IL1R2 and CTLA4. For mechanism, we found IL-1β promoted the expression of IL1R2 and CTLA4 in Tregs, and upregulated CTLA4 though NR4A1 translocation. These results revealed that IL1R2+Treg and serum IL1R2 level had potential diagnostic and prognostic value of HNSCC and combined targeting of IL1R2 and CTLA4 might be an effective strategy to inhibit tumor progression.