Integrated single-cell and spatial transcriptomic profiling reveals that CD177+ Tregs enhance immunosuppression through apoptosis and resistance to immunotherapy in hepatocellular carcinoma

Regulatory T cells (Tregs), an immunosuppressive subpopulation of CD4 + T cells, are prevalent in tumor tissues, where they impede effective antitumor immune responses and represent potential targets for immunotherapy. However, targeting tumor-infiltrating Treg cells (TiTregs) remains challenging. In this study, we identified CD177 as a biomarker specifically expressed in TiTregs but not in adjacent or peripheral Treg cells through single-cell transcriptome sequencing combined with a stringent screening strategy. These CD177 + TiTregs exhibited distinct transcriptional profiles characterized by enhanced immunosuppressive capabilities and were correlated with poor patient prognosis. Mechanistically, the apoptosis-related transcription factor REL drove the differentiation of CD177 + TiTregs, accompanied by apoptosis and enhanced immunosuppression. Furthermore, using a CD177 Treg conditional knockout mouse model, we demonstrated that…