Tyrinova Tamara, Batorov Egor, Aristova Tatyana, Ushakova Galina, Sizikova Svetlana, Denisova Vera, Chernykh Elena
Research Institute of Fundamental and Clinical Immunology, 14 Yadrintscevskaya str., Novosibirsk, 630099, Russian Federation.
Heliyon. 2024 Feb 16;10(5):e26362. doi: 10.1016/j.heliyon.2024.e26362. eCollection 2024 Mar 15.
Recent studies demonstrated that myeloid-derived suppressor cells (MDSCs) are involved in the pathogenesis and progression of multiple myeloma (MM). Nevertheless, data on the quantitative and functional changes in MDSCs during standard MM treatment remain poorly understood. Here, we determined that monocytic MDSCs (M-MDSC; CD14HLA-DR) and granulocytic MDSCs (PMN-MDSC; LinHLA-DRCD33CD66b) in MM patients in remission following induction therapy (IT) were significantly increased, while early MDSCs (E-MDSCs; LinHLA-DRCD33CD66b) were decreased compared to the donor group. In progression, MM patients had the most pronounced decrease in E-MDSCs and enhanced levels of PMN-MDSCs. IT was accompanied with a decrease in the expression of arginase-1 (Arg-1). In MM patients with relapse or resistance to IT, Arg-1 cell frequency in M-MDSCs and E-MDSCs, as well as PD-L1 M-MDSCs, was increased, which may facilitate tumor immunosuppression. G-CSF administration led to a significant increment in the MDSC subsets. At the engraftment, circulating M-MDSC and PMN-MDSCs were temporarily increased, with a gradual decline to the pre-transplant levels in 12 months. The percentage of E-MDSCs was decreased at the leukocyte recovery. Patients with a higher (>Me) M-MDSC count at the engraftment had a shorter post-transplant leukopenia duration (Me 11 vs. 13 days; p = 0.0086). The advanced MM stage, depth of response, and lower relative count of circulating E-MDSCs at the engraftment were independent risk factors associated with a lower progression-free survival. The obtained data allow us to hypothesize that MDSCs may play a positive role at the stage of leukocyte recovery by ameliorating the long-term anti-tumor response in MM.
近期研究表明，髓系来源的抑制性细胞（MDSCs）参与了多发性骨髓瘤（MM）的发病机制和进展过程。然而，关于标准MM治疗期间MDSCs的数量和功能变化的数据仍知之甚少。在此，我们确定，诱导治疗（IT）后缓解期的MM患者中，单核细胞MDSCs（M-MDSC；CD14 HLA-DR）和粒细胞MDSCs（PMN-MDSC；Lin HLA-DR CD33 CD66b）显著增加，而与供体组相比，早期MDSCs（E-MDSCs；Lin HLA-DR CD33 CD66b）减少。在疾病进展期，MM患者的E-MDSCs下降最为明显，PMN-MDSCs水平升高。IT伴随着精氨酸酶-1（Arg-1）表达的降低。在复发或对IT耐药的MM患者中，M-MDSCs和E-MDSCs中的Arg-1细胞频率以及PD-L1 M-MDSCs增加，这可能促进肿瘤免疫抑制。给予粒细胞集落刺激因子（G-CSF）导致MDSC亚群显著增加。在植入时，循环中的M-MDSC和PMN-MDSCs暂时增加，12个月后逐渐降至移植前水平。白细胞恢复时E-MDSCs的百分比降低。植入时M-MDSC计数较高（>中位数）的患者移植后白细胞减少持续时间较短（中位数11天对13天；p = 0.0086）。晚期MM分期、缓解深度以及植入时循环E-MDSCs的相对计数较低是与无进展生存期较低相关的独立危险因素。所获得的数据使我们能够推测，MDSCs可能通过改善MM中的长期抗肿瘤反应在白细胞恢复阶段发挥积极作用。
