Norcholic Acid Promotes Tumor Progression and Immune Escape by Regulating Farnesoid X Receptor in Hepatocellular Carcinoma

• DOI: 10.3389/fonc.2021.711448
• Publication Date: 2021-11-30T11:23:17Z
• Authors: Yihang Gong; Kun Li; Yunfei Qin; Kaining Zeng; Jianrong Liu; Shaozhuo Huang; Yewu Chen; Haoyuan Yu; Wei Liu; Linsen Ye; Yang Yang
• Keywords: Farnesoid X receptor; Tumor progression

Accumulating evidence shows a close association between various types of bile acids (BAs) and hepatocellular carcinoma (HCC), they have been revealed to affect tumor immune response progression mainly by regulating Farnesoid X receptor (FXR). Nevertheless, the roles Norcholic acid(NorCA) in HCC remain unknown yet. In this study, herein we demonstrate that NorCA can promote cell proliferation, migration invasion through negatively FXR. Additionally, increase PD-L1 level on surfaces cells their exosomes, NorCA-induced exosomes dramatically dampen function CD4+T cells, thereby inducing an immunosuppressive microenvironment. Meanwhile, negative correlation FXR expression human specimens was identified, patients with FXRlowPD-L1high exhibit rather dismal survival outcome. Importantly, agonist (GW4064) synergize anti-PD-1 antibody (Ab) inhibit growth tumor-bearing models. Taken together, inhibiting signaling, implying superiority combination Ab monotherapy checkpoint inhibitor combating HCC. However, more well-designed animal experiments clinical trials are warranted further confirm our findings future due limitations study.