Novel B7-H4-mediated crosstalk between human non-Hodgkin lymphoma cells and tumor-associated macrophages leads to immune evasion via secretion of IL-6 and IL-10

作者：Che, Fengyuan; Heng, Xueyuan; Zhang, Haiyan; Su, Quanping; Zhang, Baoxue; Chen, Yanying; Zhang, Zhaohong; Du, Yifeng^*; Wang, Lijuan^*

来源：Cancer Immunology, Immunotherapy, 2017, 66(6): 717-729.

DOI：10.1007/s00262-017-1961-7

• Non-Hodgkin lymphoma
• B7-H4
• Tumor-associated macrophages
• Immune evasion
• IL-6
• IL-10

Non-Hodgkin lymphoma (NHL) is an incurable lymphoproliferative cancer, and patients with NHL have a poor prognosis. The present study explored the regulatory mechanism of expression and possible roles of the immunosuppressive B7-H4 molecule in human NHL. For functional studies, NHL-reactive T cell lines were generated via the isolation of allogeneic CD3(+) T cells from healthy donors and repeated in vitro stimulation with irradiated NHL cells isolated from patients. B7-H4 was found to be distributed in NHL cells and tissues, and its surface protein expression levels were further upregulated by the incubation of NHL cells with interleukin (IL)-6, IL-10, or interferon-gamma. Additionally, the supernatants of tumor-associated macrophages (tM phi s) upregulated B7-H4 surface expression by producing IL-6 and IL-10. B7-H4 expressed in NHL cells inhibited the cytotoxic activity of NHL-reactive T cells. Conversely, the inhibition of B7-H4 in NHL cells promoted T cell immunity and sensitized NHL cells to cytolysis. Furthermore, tM phi s induced B7-H4 promoted NHL cell evasion of the T cell immune response. In conclusion, this study shows that NHL-expressed B7-H4 is an important immunosuppressive factor that inhibits host anti-tumor immunity to NHL. Targeting tumor-expressed B7-H4 may thus provide a new treatment strategy for NHL patients.

• 出版日期2017-6
• 单位临沂市人民医院; 山东省立医院; 山东大学