Activated normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from blood and bone marrow of multiple myeloma (MM) patients have the ability to suppress T-cells, as MDSC. MM is an incurable plasma cell malignancy of the bone marrow. Like most malignancies, myeloma cells alter its microenvironment to promote tumor growth, including inhibition of the immune system. We found that MM NDG from the bone marrow suppressed proliferation of T-cells, in contrast to healthy donors. The inhibitory effect could not be explained by changed levels of mature or immature NDG in the bone marrow. Moreover, NDG isolated from the blood of both myeloma patients and healthy individuals could inhibit T-cell proliferation and IFN-γ production. On the contrary to previous studies, blood NDGs did not have to be preactivated to mediate suppressive effects. Instead, they became activated during coculture, indicating that contact with activated T-cells is important for their ability to regulate T-cells. The inhibitory effect was dependent on the production of reactive oxygen species and could be reverted by the addition of its inhibitor, catalase. Our findings suggest that blood NDGs from MM patients are suppressive, but no more than NDGs from healthy donors. However, only bone marrow NDG from MM patients exhibited MDSC function. This MDSC-like suppression mediated by bone marrow NDG could be important for the growth of malignant plasma cells in MM patients.

中文翻译：

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多发性骨髓瘤患者的骨髓中性粒细胞表现出骨髓来源的抑制细胞活性

活化的正常密度粒细胞 (NDG) 可以以与髓源性抑制细胞 (MDSC) 类似的方式抑制 T 细胞反应。在这项研究中，我们检验了来自多发性骨髓瘤 (MM) 患者血液和骨髓的 NDG 具有抑制 T 细胞（如 MDSC）的能力的假设。MM是一种无法治愈的骨髓浆细胞恶性肿瘤。与大多数恶性肿瘤一样，骨髓瘤细胞会改变其微环境以促进肿瘤生长，包括抑制免疫系统。我们发现，与健康供体相比，来自骨髓的 MM NDG 抑制了 T 细胞的增殖。抑制作用不能用骨髓中成熟或未成熟 NDG 水平的变化来解释。此外，从骨髓瘤患者和健康个体的血液中分离的 NDG 可以抑制 T 细胞增殖和 IFN-γ生产。与以前的研究相反，血液 NDG 不必预先激活以介导抑制作用。相反，它们在共培养过程中被激活，这表明与激活的 T 细胞接触对于它们调节 T 细胞的能力很重要。抑制作用取决于活性氧的产生，并且可以通过添加其抑制剂过氧化氢酶来恢复。我们的研究结果表明，来自 MM 患者的血液 NDG 具有抑制性，但不超过来自健康供体的 NDG。然而，只有来自 MM 患者的骨髓 NDG 表现出 MDSC 功能。这种由骨髓NDG介导的MDSC样抑制可能对MM患者恶性浆细胞的生长很重要。