趋化因子
脾脏
癌症研究
髓源性抑制细胞
生物
趋化因子受体
转移
免疫系统
免疫学
髓样
癌症
抑制器
遗传学
作者
Baohua Li,Shu Zhang,Na Huang,Haiyan Chen,Peijun Wang,Jun Yang,Zongfang Li
摘要
Myeloid‑derived suppressor cells (MDSCs) are the major negative regulators of immune responses and expand in numerous tumor models. They contribute to tumor progression and metastasis, and are involved in limiting the effects of cancer immunotherapy. To selectively target MDSCs, it is required to understand the molecular mechanisms that drive MDSC expansion. The mechanisms of their accumulation in tumor tissue have been extensively studied, while the mechanisms of their expansion in lymphoid organs have been rarely explored. The spleen is the largest lymphoid organ in the human body. A previous study by our group reported that a negative immune status in the spleen facilitated tumor growth, with MDSCs being the major immunosuppressive cells. In the present study, a murine H22 orthotopic hepatoma model was established and the mechanisms of splenic MDSC accumulation were studied, including MDSC proliferation, apoptosis and chemotaxis. The proliferation and apoptosis of splenic MDSCs did not differ between normal and tumor‑bearing (TB) mice. Cytokine array and ELISA of splenic tissues indicated elevated chemokine (C‑C motif) ligand 9 (CCL9) levels in TB mice. Furthermore, splenic macrophages were able to secrete CCL9. Flow cytometric analysis revealed that splenic MDSCs from TB mice also overexpressed C‑C motif chemokine receptor 1 (CCR1), the receptor for CCL9. Taken together, the present results indicate that CCL9 secreted by splenic macrophages induces a CCR1‑dependent accumulation of MDSCs in the spleen in a murine H22 hepatoma model.
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