Inhibition of APOC1 promotes the transformation of M2 into M1 macrophages via the ferroptosis pathway and enhances anti-PD1 immunotherapy in hepatocellular carcinoma based on single-cell RNA sequencing

Single-cell RNA-sequencing (scRNA-seq) presents better insights into cell behavior in the context of a complex tumor microenvironment by profiling single-cell populations. However, the mechanisms underlying treatment failure in hepatocellular carcinoma (HCC) are poorly understood. In this study, we performed deep scRNA-seq on immune cells under the isolation in peripheral blood, cancer tissues, and nearby common tissues of four HCC cases and two non-cancer controls, and 212,494 cells were included in the analysis. We identified distinct immune cell subtypes, enriched pathways for differential genes, and delineated associated developmentally relevant trajectories. APOC1 was found over-expressed in tumor-associated macrophages (TAMs) of HCC tissues than in normal tissues. Inhibition of APOC1 reversed the M2 phenotype to the M1 phenotype via the ferroptosis pathway in TAMs from HCC. Tumors in APOC1