Akkermansia muciniphila might improve anti‐PD‐1 therapy against HCC by changing host bile acid metabolism

Abstract

AbstractPD‐1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD‐1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD‐1mAb against HCC in a tumor‐bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+T proportion in the tumor microenvironment. Additionally, AKK downregulates PD‐L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD‐1mAb against HCC through its impact on bile acid metabolism.