γδ T细胞受慢性淋巴细胞白血病负担的影响显著,但仅受髓系来源的抑制性细胞轻度影响。
γδ T Are Significantly Impacted by CLL Burden but Only Mildly Influenced by M-MDSCs.
作者信息
Zarobkiewicz Michał, Kowalska Wioleta, Szymańska Agata, Lehman Natalia, Kowalczyk Bożena, Tomczak Waldemar, Bojarska-Junak Agnieszka
机构信息
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.
Department of Genetics and Microbiology, Maria Curie-Sklodowska University, 20-033 Lublin, Poland.
出版信息
Cancers (Basel). 2025 Jan 14;17(2):254. doi: 10.3390/cancers17020254.
BACKGROUND/OBJECTIVES: The current study explores the impact of CLL on γδ T cells and, in an attempt to better understand the sources of immunosuppression, assesses the impact of M-MDSCs on γδ T cells in vitro.
METHODS
The study included 163 CLL patients and 34 healthy volunteers. γδ T cells were screened with flow cytometry, including NKG2D, Fas, FasL, and TRAIL staining. Additionally, to deepen understanding of the immunosuppressive impact of CLL on γδ T, a set of in vitro co-cultures of γδ T and M-MDSCs was performed.
RESULTS
RNAseq revealed significant, though relatively minor, changes in the transcriptome. Functional analyses showed a minor drop in cytotoxic potential against CLL cells. Finally, depletion of M-MDSCs from CLL-derived peripheral blood mononuclear cells did not restore γδ T cells' proliferative response.
CONCLUSIONS
Altogether, this suggests a minor impact of M-MDSCs on activated γδ T. Thus, it seems probable that other mechanisms than M-MDSCs mediate the negative impact of CLL on circulating γδ T cells.
背景/目的:本研究探讨慢性淋巴细胞白血病(CLL)对γδT细胞的影响,并为更好地理解免疫抑制的来源,评估单核细胞来源的髓系抑制细胞(M-MDSCs)在体外对γδT细胞的影响。
方法
本研究纳入了163例CLL患者和34名健康志愿者。采用流式细胞术对γδT细胞进行筛选,包括自然杀伤细胞2D(NKG2D)、Fas、Fas配体(FasL)和肿瘤坏死因子相关凋亡诱导配体(TRAIL)染色。此外,为了更深入地了解CLL对γδT细胞的免疫抑制作用,进行了一组γδT细胞与M-MDSCs的体外共培养实验。
结果
RNA测序显示转录组有显著但相对较小的变化。功能分析表明,对CLL细胞的细胞毒性潜力略有下降。最后,从CLL来源的外周血单个核细胞中去除M-MDSCs并不能恢复γδT细胞的增殖反应。
结论
总体而言,这表明M-MDSCs对活化的γδT细胞影响较小。因此,除M-MDSCs外,可能还有其他机制介导CLL对循环γδT细胞的负面影响。