a Department of Gastroenterology, Shanghai Ninth People's Hospital, School of Medicine , Shanghai Jiaotong University , Shanghai , P.R. China.
b Department of Surgery, Shanghai Ninth People's Hospital, School of Medicine , Shanghai Jiaotong University , Shanghai , P.R. China.
Immunopharmacol Immunotoxicol. 2018 Feb;40(1):91-97. doi: 10.1080/08923973.2017.1417997. Epub 2018 Jan 5.
Myeloid derived suppressor cells (MDSC) play an important role in tumor immune evasion and its level significantly increased in patients with gastric cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCR5 level in gastric cancer.
G-MDSC and M-MDSC from the peripheral blood and tumor parenchyma were analyzed by flow cytometry. CCR5 ligand CCL5 was detected by ELISA. CCR5 was detected by real-time PCR, western blot and flow cytometry. Furthermore, the therapeutic effects of CCR5 blockade was assessed by the tumor model.
CCR5 ligand, gene and protein expression of CCR5, and surface expression of CCR5 significantly increased in blood and tumor of tumor-bearing mice, suggesting MDSC may be attracted into the parenchyma by CCL5/CCR5. Anti-CCR5 treatment decreased G-MDSC and M-MDSC in the periphery and tumor. In addition, combination treatment enhanced CD4+ and CD8+ T cell infiltration and decreased the tumor burden of tumor-bearing mice.
This study elucidated a possible association between MDSC subsets and CCR5, in addition to provide a new potential target to enhance the efficacy of immunotherapy in patients with gastric cancer.
髓系来源抑制细胞（MDSC）在肿瘤免疫逃逸中发挥重要作用，其在胃癌患者中的水平显著升高。研究证实了 MDSC 与外周血中各种细胞因子之间的关联。然而，关于 MDSC 进入肿瘤实质的机制知之甚少。本研究旨在分析胃癌患者 MDSC 亚群与 CCR5 水平之间的相关性。
通过流式细胞术分析外周血和肿瘤实质中的 G-MDSC 和 M-MDSC。通过 ELISA 检测 CCR5 配体 CCL5。通过实时 PCR、western blot 和流式细胞术检测 CCR5。此外，通过肿瘤模型评估 CCR5 阻断的治疗效果。
在荷瘤小鼠的血液和肿瘤中，CCR5 配体、CCR5 基因和蛋白表达以及 CCR5 表面表达均显著增加，提示 MDSC 可能通过 CCL5/CCR5 被吸引到实质中。抗 CCR5 治疗可减少外周血和肿瘤中的 G-MDSC 和 M-MDSC。此外，联合治疗可增强 CD4+和 CD8+T 细胞浸润并降低荷瘤小鼠的肿瘤负担。
本研究阐明了 MDSC 亚群与 CCR5 之间可能存在关联，并为增强胃癌患者免疫治疗的疗效提供了一个新的潜在靶点。
