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多发性骨髓瘤患者移植后中性粒细胞减少期骨髓来源抑制细胞、TIM-3+ T细胞与临床因素之间的关联

Associations Between Myeloid-Derived Suppressor Cells, TIM-3+ T Cells, and Clinical Factors During the Post-transplant Neutropenia Period in Patients With Multiple Myeloma.

作者信息

Batorov Egor, Tyrinova Tamara, Aristova Tatyana, Denisova Vera, Batorova Dariya, Sizikova Svetlana, Ushakova Galina, Ostanin Aleksandr, Chernykh Elena

机构信息

Laboratory of Cellular Immunotherapy, Research Institute of Fundamental and Clinical Immunology, Novosibirsk, RUS.

Department of Immunology, Vladimir Zelman Institute for Medicine and Psychology, Novosibirsk National Research State University, Novosibirsk, RUS.

出版信息

Cureus. 2025 Jun 24;17(6):e86641. doi: 10.7759/cureus.86641. eCollection 2025 Jun.

Abstract

INTRODUCTION

The objective of our study was to assess relationships between circulating myeloid-derived suppressor cell (MDSC) populations and T cell subsets, up-regulating PD-1 and TIM-3, as well as their intended association with several post-transplant clinical factors.

METHODS

Forty-five patients with multiple myeloma (MM) were enrolled in the study. Circulating LinHLA-DRCD33CD66b polymorphonuclear (PMN) MDSCs, CD14HLA-DR monocytic (M) MDSCs, PD-1/TIM-3 CD4 and CD8 T cells were assessed with flow cytometry at the engraftment and following six post-transplant months. The frequencies of patients with common post-transplant complications, antibacterial treatment, and granulocyte colony-stimulating factor (G-CSF) administration during the neutropenia period were investigated.

RESULTS

TIM-3 CD4 and CD8 T cell counts were negatively associated with M-MDSCs at the engraftment. Both PD-1/TIM-3 T cells and MDSCs at the engraftment did not differ between the patients with or without febrile episodes, oral mucositis, and enteropathy during the neutropenia period. Relative counts of PMN-MDSCs were significantly lower in MM patients who received carbapenems compared to those treated with cefepime. Short-term G-CSF administration was associated with an increase in M-MDSCs.

CONCLUSION

Following autologous hematopoietic stem cell transplantation (HSCT), cellular interactions and the possible impact of therapeutic interventions on the immune recovery have not been fully investigated and may be of interest as predictive biomarkers and targets for novel therapies.

摘要

引言

我们研究的目的是评估循环髓系来源抑制细胞(MDSC)群体与T细胞亚群之间的关系,这些T细胞亚群上调程序性死亡受体1(PD-1)和T细胞免疫球蛋白黏蛋白分子3(TIM-3),以及它们与几种移植后临床因素的预期关联。

方法

45例多发性骨髓瘤(MM)患者纳入本研究。在植入时以及移植后6个月,采用流式细胞术评估循环中淋巴细胞系人白细胞抗原-DR(LinHLA-DR)阴性、CD33阳性、CD66b阳性的多形核(PMN)MDSC、CD14阳性、HLA-DR阴性的单核细胞(M)MDSC、PD-1/TIM-3 CD4和CD8 T细胞。调查了移植后常见并发症患者的发生率、抗菌治疗情况以及中性粒细胞减少期粒细胞集落刺激因子(G-CSF)的使用情况。

结果

植入时,TIM-3 CD4和CD8 T细胞计数与M-MDSC呈负相关。中性粒细胞减少期有或无发热、口腔黏膜炎和肠病的患者,植入时PD-1/TIM-3 T细胞和MDSC均无差异。与接受头孢吡肟治疗的MM患者相比,接受碳青霉烯类药物治疗的患者PMN-MDSC的相对计数显著降低。短期使用G-CSF与M-MDSC增加有关。

结论

自体造血干细胞移植(HSCT)后,细胞间相互作用以及治疗干预对免疫恢复的可能影响尚未得到充分研究,作为预测生物标志物和新疗法靶点可能具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b1e7/12287756/074135618a1a/cureus-0017-00000086641-i01.jpg

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