Integrating single-cell and spatial transcriptomics to elucidate the cross-talk of SPP1+ macrophage and cancer associated fibroblast in HCC with immune excluded microenvironment

we comprehensively analyzed 38,439 cells from six HCC tumor tissues and 45,354 cells from matched adjacent normal tissues to reveal the cellular composition of HCC at single cell resolution. Importantly, we found SPP1+ macrophage in TME was indicative of poor patient survival. Then, we performed ST analysis, importantly we found SPP1+ macrophage colocalized with CAF and wrapped around the edge of tumor. Then we explore the possible interaction between SPP1+ macrophage and malignant hepatocytes and found malignant cells could alter the function of SPP1+ macrophage through hypoxia. We further evaluate the infiltration of SPP1+ macrophage and CAF in several independent HCC cohorts with bulk transcriptomics using our scRNA-seq as reference transcriptomics matrix and revealed a close correlation of the infiltration between these two cell subtypes. In addition, the colocalization of SPP1+ macrophage and CAF could limit the infiltration of immune cells in tumor core through promoting the extracellular matrix expression and stimulating the formation of the desmoplastic region.