Microvesículas circulantes derivadas de células T regulatórias e sua influência na imunossupressão celular em pacientes pediátricos com Leucemia Linfoblástica Aguda de células B submetidos a quimioterapia de remissão

Abstract

Microvesicles (MVs) are important mediators of intercellular communication and can play an important role in both the hematopoietic microenvironment and blood circulation. Furthermore, recent studies have demonstrated that MVs derived from regulatory T cells (Treg) may be associated with the promotion of an immunosuppressive microenvironment with repercussions in the periphery, contributing to tumor progression. Thus, the present study aimed to characterize the profile of circulating MVs derived from regulatory T cells (MVs-Treg) and immunosuppressive cytokines in pediatric patients with B-cell Acute Lymphoblastic Leukemia (B-ALL) undergoing remission chemotherapy. A descriptive, prospective longitudinal study was carried out with 20 peripheral blood samples from pediatric patients diagnosed with B-ALL collected at four moments of remission induction therapy, referred to as: day of diagnosis (D0), day 8 (D8), day 15 (D15) and end of remission induction therapy (D35). In addition, samples from 20 children without leukemia were included, who made up the control group (CG). Subsequently, immunophenotyping of Treg lymphocytes was performed, as well as immunophenotypic characterization of MVs-Treg, using the FACSCalibur (BD Biosciences) and CytoFLEX (Beckman Coulter) cytometers, respectively. In parallel, the quantification of the cytokines TGF-β and IL-10 was carried out with the ProQuantum and Cytometric Bead Array (CBA) kits, respectively. Our results demonstrated that patients with B-ALL present, on D0, an increase in IL-10 and a decrease in TGF-β, together with a trend towards an increase in MVs-CD152+ (CTLA-4). Furthermore, a decrease in Treg lymphocytes was observed on D8 and D15. Finally, a decrease in IL-10, MVs-CD25+ and CD152+ was noted, with an increase in TGF-β and CD4+ T lymphocytes and Tregs. In conclusion, our findings demonstrate an immunosuppressive process at D0, a possible transition of the immunological response profile during treatment. Furthermore, to our knowledge, this is the first study that describes the kinetics of Treg lymphocytes, MVs-Tregs (CD4+, CD25+ and CD152+) and the cytokines IL-10 and TGF-β during the entire period of remission induction therapy in pediatric patients with B-ALL.