Department of Immunology and Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt.
Department of Surgery, Vascular Surgery Unit, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Asian Pac J Cancer Prev. 2020 Nov 1;21(11):3393-3403. doi: 10.31557/APJCP.2020.21.11.3393.
Accumulation of myeloid-derived suppressor cells (MDSCs) constitutes a key mechanism of tumor immune evasion in gastric cancer (GC). Therefore, searching for more accurate prognostic factors affecting their immunosuppressive role has become a growing interest in cancer immunotherapy research. Increased expression of microRNA-494 was noticed in MDSCs from tumor-bearing mice, suggesting another new therapeutic objective for cancer treatment. It was also discovered that tumor-derived transforming growth factor beta (TGF-β) is responsible for the up-regulation of microRNA-494 in MDSCs. The purpose of this study was to address the effect of recombinant (rTGF-β) on the anti-inflammatory activity of MDSCs in GC and its possible association with micro-RNA-494 expression in tumor tissue.
Freshly obtained GC tumor tissue samples and peripheral blood were used for isolation of CD33+11b+HLADR- MDSCs cells from 40 GC patients and 31 corresponding controls using flow cytometry. MDSCs were co-cultured with isolated autologous T cells to assess proliferation and cytokine production in the presence and absence of rTGF-β. Real-time PCR and Enzyme linked immunosorbent assay were used to evaluate tumor expression of miRNA-494 and TGF-β respectively.
Results showed that rTGF-β markedly increased the suppressive ability of tumor MDSCs on proliferation of autologous T cells and interferon gamma production. However, no inhibitory effect was observed for MDSCs from circulation. In addition, infiltration of MDSCs in tumors is associated with the prognosis of GC. MiRNA-494 was also extensively expressed in tumor samples with a significant correlation to MDSCs.
These results indicate that tumor-derived MDSCs but not circulatory MDSCs have an immunosuppressive effect on T cells, potentially involving TGF-β mediated stimulation. Results also suggest a role for miRNA-494 in GC progression. Therefore, control of TGF-β and miRNA-494 may be used as a treatment strategy to downregulate the immunosuppressive effect of MDSCs.
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髓系来源的抑制性细胞（MDSCs）的积累构成了胃癌（GC）中肿瘤免疫逃逸的关键机制。因此，寻找更准确的影响其免疫抑制作用的预后因素已成为癌症免疫治疗研究的一个新的关注点。在荷瘤小鼠的 MDSCs 中观察到 microRNA-494 的表达增加，这表明癌症治疗的另一个新的治疗目标。还发现肿瘤衍生的转化生长因子β（TGF-β）负责 MDSCs 中 microRNA-494 的上调。本研究旨在探讨重组（rTGF-β）对 GC 中 MDSCs 抗炎活性的影响及其与肿瘤组织中 microRNA-494 表达的可能相关性。
使用流式细胞术从 40 名 GC 患者和 31 名相应对照的新鲜获得的 GC 肿瘤组织样本和外周血中分离 CD33+11b+HLADR-MDSCs 细胞。将 MDSCs 与分离的自体 T 细胞共培养，以评估 rTGF-β 存在和不存在时 T 细胞的增殖和细胞因子产生。使用实时 PCR 和酶联免疫吸附试验分别评估肿瘤中 miRNA-494 和 TGF-β 的表达。
结果表明，rTGF-β 显著增加了肿瘤 MDSCs 对自体 T 细胞增殖和干扰素γ产生的抑制能力。然而，循环中的 MDSCs 没有观察到抑制作用。此外，MDSCs 在肿瘤中的浸润与 GC 的预后相关。miRNA-494 也广泛表达在肿瘤样本中，与 MDSCs 有显著相关性。
这些结果表明，肿瘤来源的 MDSCs 而不是循环中的 MDSCs 对 T 细胞具有免疫抑制作用，可能涉及 TGF-β 介导的刺激。结果还表明 miRNA-494 在 GC 进展中起作用。因此，控制 TGF-β 和 miRNA-494 可能被用作下调 MDSCs 免疫抑制作用的治疗策略。
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