Integrative single-cell RNA and T-cell receptor analyses reveal transcriptional features of antigen-reactive tumor-infiltrating regulatory T cells in patients with lung cancer

ABSTRACT: Background: T-cell receptor (TCR) stimulation is essential to complete differentiation of tumor-infiltrating regulatory T cells (T-Tregs). Therefore, elucidation of TCR-dependent regulatory network involved in activation and proliferation of T-Tregs will facilitate discovery of novel antitumor remedy. Here, we investigated transcriptional features specific for antigen-reactive Tregs by harnessing single-cell RNA and TCR analyses of human Tregs derived from patients with non-small cell lung cancer (NSCLC). Methods: Assuming Tregs undergo clonal expansion in response to antigens, we sought for transcriptional features specific for antigen-reactive Tregs by comparing gene expression of Tregs with unique TCR clonotypes and those with expanded TCR clonotypes. To verify the identified molecule, multiplex immunohistochemistry and flow cytometry were used. Results: We found that the proportion of Tregs with expanded clonotypes was much higher in the tumor than in the periphery blood. We also found that T-Tregs with shared clonotypes were transcriptionally more similar to each other than to those with different clonotypes. Finally, we identified SYNGR2, TNFRSF18, DUSP4, and CTLA4 as core signature genes for T-Tregs with expanded clonotypes and confirmed their existences expressed on human T-Tregs. Interestingly, T-Treg-specific co-regulatory network revealed that SYNGR2, TNFRSF18 and DUSP4 are potential coordinators between TCR-dependent activation and cell proliferation. Conclusions: Our study shed light on regulatory insights of TCR-dependent Treg activation and differentiation in tumor and therapeutic strategies for patients with NSCLC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE164146 | GEO | 2023/01/01

REPOSITORIES: GEO