期刊
BIOCHEMICAL PHARMACOLOGY
卷 188, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2021.114576
关键词
Diffuse large B-cell lymphoma; Berberine; CD47; Phagocytosis; Immunochemotherapy
资金
- National Natural Science Foundation [81800194, 82070203, 81770210, 81473486, 81270598]
- Key Research and Development Program of Shandong Province [2018CXGC1213]
- Development Project of Youth Innovation Teams in Colleges and Universities of Shandong Province [2020KJL006]
- China Postdoctoral Science Foundation [2020M672103]
- Technology Development Projects of Shandong Province [2017GSF18189]
- Translational Research Grant of NCRCH [2021WWB02, 2020ZKMB01]
- Shandong Provincial Natural Science Foundation [ZR2018BH011]
- Technology Development Project of Jinan City [201805065]
- Taishan Scholars Program of Shandong Province
- Shandong Provincial Engineering Research Center of Lymphoma
- Academic Promotion Programme of Shandong First Medical University [2019QL018, 2020RC006]
This study revealed that berberine could suppress CD47 expression in DLBCL, enhance macrophage phagocytosis, and improve the efficacy of anti-CD47 antibody and rituximab. The establishment of a prognostic model based on CD47 and CD68 provided novel insights into DLBCL treatment and potential therapeutics.
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) with high clinical heterogeneity and poor prognosis. Immune escape mediated by CD47 overexpression contributes to the limited efficacy of rituximab, an anti-CD20 antibody, which indicates a target to improve the efficacy of DLBCL treatment. Here, we validated berberine, a natural compound, as a suppressor of CD47 and revealed the involved mechanism and biological function in DLBCL. Berberine downregulated the expression of CD47 in DLBCL at the transcriptional level by suppressing c-myc expression. Berberine-induced CD47 inhibition enhanced the phagocytosis of macrophages, thereby eliminating DLBCL cells in vitro and in vivo. Interestingly, berberine enhanced the efficiency of anti-CD47 antibody and rituximab-mediated phagocytosis. Moreover, a novel prognostic model based on the combination of CD47 and CD68, a biomarker of macrophages, was established in DLBCL. Our results highlighted for the first time that berberine could restore macrophage function in the tumor microenvironment, enhance rituximab-mediated phagocytosis and promote anti-CD47 antibody function via suppressing CD47 expression, which revealed a new anti-tumor mechanism of berberine and provided novel insights into the rituximab-based immunochemotherapy and CD47-targeted immunotherapy in DLBCL.
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