Description: Immunotyping based on T cells, particularly the priming and recruitment of cytotoxic T lymphocytes (CTLs), has demonstrated clinical benefits in hepatocellular carcinoma (HCC) and other solid tumors. However, a significant proportion of CTL-rich HCCs exhibit early relapse or immunotherapy resistance, highlighting the heterogeneity within this subgroup. Here, we dissected the immune landscapes and spatial architectures of CTL-rich HCCs. Random forest and Cox regression models identified macrophage aggregation as a distinctive spatial pattern that characterizes a subset of CTL-rich HCCs with immunosuppressive microenvironment and poor prognosis. Integrated analysis of single-cell and spatial transcriptomics, combined with in vitro macrophage cultures, revealed that spatial aggregation promoted macrophage reprogramming towards a pro-tumoral phenotype in HCC. Consequently, HCCs characterized by increased macrophage aggregation exhibited elevated PD-1+LAG3+ exhausted CTLs adjacent to macrophage-aggregates and potentially higher response rates to immunotherapy suggested by multiple molecular signatures and retrospective analyses. These findings suggest macrophage spatial distribution as a promising biomarker for HCC immunotyping with significant prognostic and therapeutic implications.

Data type: Transcriptome or Gene expression

Sample scope: Monoisolate

Relevance: Medical

Release date: 2024-05-30

Last updated: 2024-05-30

Data size: 33.01GB