Dreisinger Mojca, Roškar Zlatko, Goropevšek Aleš, Zakelšek Andreja, Čurič Sara, Živko Nada, Bevc Sebastjan, Homšak Evgenija
Department of Haematology, University Medical Centre Maribor, 2000 Maribor, Slovenia.
Department of Laboratory Diagnostics, University Medical Centre Maribor, 2000 Maribor, Slovenia.
Biomedicines. 2025 May 15;13(5):1204. doi: 10.3390/biomedicines13051204.
: In mouse models of chronic lymphocytic leukemia (CLL), an effective anti-leukemia immune response was obtained by depleting a specific regulatory T-cell (Treg) subset. While STAT5 signaling could alter the homeostasis of naïve (nTreg) and activated (aTreg) subsets, which are capable of suppressing also CLL patients' responses to microbial antigens, perturbed STAT3 signaling could drive CXCR5 expression in circulating T-follicular regulatory cells (Tfr) and their entry into the lymph node/tumor microenvironment. : By using phospho-specific flow cytometry, we monitored STAT signaling/phosphorylation (pSTAT), in vitro responses to Sars-Cov2-antigen-specific stimulation, and circulating Treg subsets in relation to Binet stage and total tumor mass/tumor distribution (TTM/TD) scoring in 62 patients with CLL. : The percentage of CXCR5 Treg significantly increased in patients with Binet stage B disease, and Tfr-like subsets were associated with higher TTM and lower TD. The pSTAT3 levels in CD4 T-cells were only significantly increased in patients undergoing therapy. Lower nTreg percentages correlated with increased disease duration, and an increased aTreg/nTreg ratio correlated with SARS-CoV-2-antigen-induced STAT5 signaling responses. : The results show increased amounts of circulating CXCR5 Tfr-like subsets in patients with extensive lymph node involvement and augmented STAT3 signaling in patients on therapy. While STAT5 responses may drive nTreg differentiation into aTreg, nTreg decline is associated with increased disease duration.
在慢性淋巴细胞白血病（CLL）小鼠模型中，通过消耗特定的调节性T细胞（Treg）亚群获得了有效的抗白血病免疫反应。虽然STAT5信号传导可以改变天然（nTreg）和活化（aTreg）亚群的稳态，这两种亚群也能够抑制CLL患者对微生物抗原的反应，但STAT3信号传导紊乱可能会驱动循环滤泡调节性T细胞（Tfr）中CXCR5的表达及其进入淋巴结/肿瘤微环境。通过使用磷酸特异性流式细胞术，我们监测了62例CLL患者中STAT信号传导/磷酸化（pSTAT）、对Sars-Cov2抗原特异性刺激的体外反应以及与Binet分期和总肿瘤质量/肿瘤分布（TTM/TD）评分相关的循环Treg亚群。Binet分期为B期疾病的患者中CXCR5 Treg的百分比显著增加，Tfr样亚群与较高的TTM和较低的TD相关。仅接受治疗的患者CD4 T细胞中的pSTAT3水平显著增加。较低的nTreg百分比与疾病持续时间增加相关，而aTreg/nTreg比率增加与SARS-CoV-2抗原诱导的STAT5信号反应相关。结果显示，广泛淋巴结受累的患者中循环CXCR5 Tfr样亚群数量增加，接受治疗的患者中STAT3信号增强。虽然STAT5反应可能会驱动nTreg分化为aTreg，但nTreg数量下降与疾病持续时间增加相关。
