Amphotericin B suppresses M2 phenotypes and B7-H1 expression in macrophages to prevent Raji cell proliferation

• Main Authors: Jing Zhang, Dongqing Cao, Shuangquan Yu, Lingchao Chen, Daolin Wei, Chang Shen, Lin Zhuang, Qian Wang, Xiaoping Xu, Yin Tong
• Format: Article
• Language: English
• Published: BMC 2018-04-01
• Series: BMC Cancer
• Subjects: Macrophage; Burkitt’s lymphoma; Amphotericin B; B7-H1
• Online Access: http://link.springer.com/article/10.1186/s12885-018-4266-0

Abstract Background Macrophages in the tumor microenvironment play a critical role in tumorigenesis and anti-cancer drug resistance. Burkitt’s lymphoma (BL) is a B-cell non-Hodgkin’s lymphoma with dense macrophage infiltration. However, the role for macrophages in BL remains largely unknown. Methods B7-H1, a transmembrane glycoprotein in the B7 family, suppresses T cell activation and proliferation and induces the apoptosis of activated T cells. The expression of B7-H1 in BL clinical tissues was determined by streptavidin-peroxidase immunohistochemistry. The mutual regulation between macrophages and BL Raji cells was investigated in a co-culture system. The cell proliferation and cell cycle distribution of Raji cells were determined using BrdU staining coupled with flow cytometry. CD163, CD204 and B7-H1 expression was assessed by flow cytometry and Western blot. Cell invasion was analyzed by Transwell assay. The expression of cytokines was detected by quantitative RT-PCR. Immunofluorescence and allogeneic T-cell proliferation assays were used to compare the expression of B7-H1, p-STAT6, or p-STAT3 and CD3+ T cell proliferation treated with or without amphotericin B. Results B7-H1 was highly expressed in tumor infiltration macrophages in most clinical BL tissues. In vitro, Raji cells synthesized IL-4, IL-6, IL-10 and IL-13 to induce CD163, CD204 and B7-H1 expression in co-cultured macrophages, which in turn promoted Raji cell proliferation and invasion. Interestingly, antifungal agent amphotericin B not only inhibited STAT6 phosphorylation to suppress the M2 polarization of macrophages, but also promoted CD3+ T cell proliferation by regulating B7-H1 protein expression in macrophages. Conclusion Amphotericin B might represent a novel immunotherapeutic approach to treat patients with BL.