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对γδ T细胞的影响,并尝试通过体外评估M-MDSCs对γδ T细胞的作用以深入理解免疫抑制的来源。方法。研究纳入163例慢性淋巴细胞白血病患者及34名健康志愿者。采用流式细胞术检测γδ T细胞,包括NKG2D、Fas、FasL和TRAIL染色分析。此外,为深入探究慢性淋巴细胞白血病对γδ T细胞的免疫抑制影响,进行了γδ T细胞与M-MDSCs的体外共培养实验。结果。RNA测序显示转录组发生显著但相对轻微的变化。功能分析表明γδ T细胞对慢性淋巴细胞白血病细胞的细胞毒性潜能略有下降。最后,清除慢性淋巴细胞白血病来源外周血单个核细胞中的M-MDSCs并未恢复γδ T细胞的增殖反应。结论。总体而言,这些结果表明M-MDSCs对活化γδ T细胞的影响有限。因此,慢性淋巴细胞白血病对循环γδ T细胞的负面调控可能主要通过M-MDSCs以外的其他机制介导。
γδ T Are Significantly Impacted by CLL Burden but Only Mildly Influenced by M-MDSCs