Preprint Article Version 1 This version is not peer-reviewed

Increased Frequency of Circulating Activated FOXP3+ Regulatory T-cell Subset in Patients with Chronic Lymphocytic Leukemia Is Associated with the Estimate of the Size of the Tumor Mass, STAT5 Signaling and Disease Course during Follow-Up of Patients

Version 1 : Received: 21 August 2024 / Approved: 21 August 2024 / Online: 21 August 2024 (16:59:32 CEST)

How to cite: Roškar, Z.; Dreisinger, M.; Homšak, E.; Avčin, T.; Bevc, S.; Goropevšek, A. Increased Frequency of Circulating Activated FOXP3+ Regulatory T-cell Subset in Patients with Chronic Lymphocytic Leukemia Is Associated with the Estimate of the Size of the Tumor Mass, STAT5 Signaling and Disease Course during Follow-Up of Patients. Preprints 2024, 2024081596. https://doi.org/10.20944/preprints202408.1596.v1 Roškar, Z.; Dreisinger, M.; Homšak, E.; Avčin, T.; Bevc, S.; Goropevšek, A. Increased Frequency of Circulating Activated FOXP3+ Regulatory T-cell Subset in Patients with Chronic Lymphocytic Leukemia Is Associated with the Estimate of the Size of the Tumor Mass, STAT5 Signaling and Disease Course during Follow-Up of Patients. Preprints 2024, 2024081596. https://doi.org/10.20944/preprints202408.1596.v1

Abstract

Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regula-tory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to en-tail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA-FOXP3high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic sig-naling in Treg subsets. Therefore, in this study, by using conventional and imaging flow cytome-try, we monitored STAT5 signaling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and disease course during follow-up of 37 patients with CLL. aTreg percentage was significantly increased among CD4+ T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4+FOXP3+ T cells at the start of therapy was character-ized by more frequent episodes of severe infections during follow-up, suggesting that aTreg frac-tion could represent a possible marker of severe disease course with infectious complications. Augmented homeostatic STAT5 signaling could support aTreg expansion, as higher pSTAT5 lev-els were significantly corelated with increased aTreg frequency among CD4+FOXP3+ T cells during follow-up of patients on therapy as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

Keywords

Chronic lymphocytic leukemia (CLL); Signal Transduction; Cytokines; T Cells

Subject

Medicine and Pharmacology, Hematology

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