Single-cell transcriptomics reveals ADRB1 as a key immune checkpoint regulating T cell exhaustion in lung cancer and its prognostic value in lung cancer.

BACKGROUND: T cells. Kaplan-Meier survival analysis and univariate Cox regression were used to study the signature of ADRB1 + T cells for prognostic value. RESULTS: scRNA-seq data confirm the presence of exhausted markers in ADRB1 + T cells. The higher proportion in LUAD tumors as compared to LUSC was linked to more pronounced immune suppression and decreased T cell diversity. CellChat predicted extensive contacts between ADRB1 + T cells and macrophages, mainly through CCL and IFN-II signaling pathways. Inferred CNV evidenced evidence of malignant cells interacting with ADRB1 + T cells. In prognostic modeling based on ADRB1 + T cell signatures, high-risk populations were characterized by very poor overall survival, and ADRB1 was an independent prognostic factor in LUAD and LUSC. CONCLUSION: This paper describes ADRB1 for the first time as a novel immune checkpoint involved in T cell exhaustion in lung cancer. Indeed, ADRB1 + T cells are promising biomarker candidates; they may even become therapeutic targets in lung cancer. Indeed, proposing a pathway by which ADRB1 may be targeted, anti-tumor immunity may be boosted and better patient prognosis secured. Thus, functional studies and clinical trials will have to be done to test and discuss this proposed concept under a new heading in therapeutic strategy.