Single-cell Sequencing Immune Landscape of Hepatocellular Carcinoma after Transarterial Chemoembolization

We performed scRNA and scTCR sequencing to dissect the immune microenvironment in both primary untreated and TACE-treated patients. We examined 54552 immune cells from 5 primary and 5 post-TACE HCC patients (5 vs 5). We found that myeloid derived cells were increased and CD8+ T cells were reduced in the microenvironment of TACE tumor samples (TT), compared with those in primary tumors (PT). More importantly, TAMs in TT samples exhibit stronger ability of complement activation, phagocytosis, angiogenesis and vasculature development function compared with PT samples, as well as an impaired function of cDC cells. In addition, the number of CD8+ T cells in TT was decreased, characterized by lower co-stimulation, cytotoxicity and exhaustion, as well as poor clonal expansion status. Interestingly, CD4+ T cells were not affected much by TACE therapy, suggesting an association with poor prognosis. We verified these findings using immunohistochemical (IHC) staining, flow cytometry and clinical prognosis analysis by TCGA database. Our study also found the reduced CXCL9 secreted by myeloid cells and decreased integrin molecules on CD8+ T cells, may potentially inhibit the infiltration of CD8+ T cells after TACE therapy. Our study revealed the immune landscape of HCC after TACE therapy, and also found the underlying mechanism of immune suppression, which will guide the development of novel strategies of immunotherapy before or after TACE treatment to benefit more for HCC patients.