期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 154, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113543
关键词
Fibrosis; Hepatocellular carcinoma; Immunomodulation; Macrophage polarization
资金
- National Natural Science Foundation of China, China [81973563, 82004029]
- Beijing Nova Program, China [Z201100006820025, Z211100002121167]
The study shows that the total tannin fraction of Terminalia bellirica (TB-TF) can inhibit hepatocellular carcinoma growth, promote the polarization of tumor-associated macrophages towards an anti-tumor phenotype, increase T cell infiltration, and restore cytotoxic function of CD8+T cells.
Tumor-associated macrophages (TAMs) are the major immunosuppressive components infiltrating the tumor microenvironment (TME). Targeting TAMs has emerged as a promising strategy to remodel immunosuppressive TME and enhance T-cell mediated anti-tumor immunity for cancer therapy. In this study, we investigate the effect and mechanism of total tannin fraction of Terminalia bellirica (Gaertn.) Roxb. (TB-TF) against hepatocellular carcinoma (HCC) using established Hepa1-6 orthotopic mouse model and murine bone marrow derived macrophage polarization model. Here we showed that TB-TF significantly inhibited orthotopic tumor growth and promoted the polarization of M2-TAMs toward the anti-tumor M1 phenotype in vivo. Further studies showed that TB-TF reversed tumor-conditioned medium induced M2 polarization of macrophages as indicated by increased expression of TNF-alpha, IL-1 beta, and iNOS, and decreased expression of Arg-1, thereby re-educating macrophages cocultured with tumor-conditioned medium into M1 phenotype. In addition, we found that TB-TF also promoted T cell infiltration mediated by chemokines such as CCL5 and CXCL10, and restored the cytotoxic function of CD8+T cells as evidenced by upregulated expression of Granzyme B, Perforin, and IFN-gamma. Our data suggest TB-TF as a promising anti-cancer agent, mediates its anti-tumor effects via remodeling the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy for hepatocellular carcinoma.
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