Randomized trial uncovers CR1's role in promoting immunosuppressive conditions in hepatocellular carcinoma, suggesting new therapeutic strategies.
Key Points
This research investigates the role of complement receptor 1 (CR1) in driving immunosuppressive tumor-associated macrophage (TAM) dysfunction in hepatocellular carcinoma (HCC).
Utilized integrative genetic and multi-omics framework including Mendelian randomization and metabolite mediation analyses.
Analyzed data from TCGA-HCC cohort, single-cell RNA-sequencing of 53,474 cells, and spatial transcriptomic sections.
Conducted functional assays in macrophages with CR1 gain- and loss-of-function, including phagocytosis and T-cell co-culture experiments.
MR analyses indicated that CR1 is linked to HCC susceptibility (IVW OR = 1.403, p = 0.017).
CR1-high tumors displayed increased M2-like macrophages and decreased CD8 + T-cell infiltration, correlating with poorer survival outcomes.
Functional assays showed CR1 overexpression led to enhanced M2 polarization and suppressed CD8 + T-cell activity.