Intestinal Akkermansia muciniphila complements the therapeutic efficacy of PD1 therapy by reshaping the immunosuppressive microenvironment in nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma [scRNA-Seq]

Using scRNA-seq coupled with immunoprofiling analyses, we found that Akk decreased the populations of immunosuppressive cells, including monocytic myeloid-derived suppressor cells (m-MDSCs) and M2 macrophages, by suppressing the differentiation of these cells from monocytes, which led to T-cell proliferation and activation. C57BL/6 mice were fed orally with 5x10^9 CFU of Akk or control PBS for 2 weeks prior to the start of the MCD diet for 2 weeks followed by orthotopic implantation of luciferase labelled RIL-175 cells for establishment NAFLD-induced HCC mouse model. The treatment continued in the period of MCD diet. After orthotopic transplantation, feeding of Akk was paused for 6 days to allow mice to recover from surgery, and the treatment was resumed until the end of the experiment. CD45+ cells from tumors treated with either Akk or PBS were extracted for studying the effect of Akk on the regulation of innate immunity in the tumor microenvironment using single RNA sequencing.