Caracterização do Perfil Fenotípico-Funcional de Células T γδ em Pacientes Pediátricos com Leucemia Linfoblástica Aguda de células B

Abstract

B-cell acute lymphoblastic leukemia (B-ALL) is the most common type of childhood cancer, characterized by the high presence of leukemic cells in the bone marrow (BM) and peripheral blood (PB), leading to the recruitment of immune cells that may contribute to tumor control. While alpha-beta (αβ) T cells are strongly affected by the disease, gamma-delta (γδ) T cells are cytotoxic and less susceptible to exhaustion, but their functional relevance in leukemia remains elusive. This work aimed to characterize the phenotypic and functional profile of γδ T cells in pediatric patients with B-ALL undergoing remission chemotherapy. It is an exploratory, longitudinal, and prospective study, carried out at the Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) in partnership with the Instituto René Rachou - Fundação Oswaldo Cruz (IRR-Fiocruz Minas). Using BM and PB samples from pediatric patients with B-ALL, obtained during chemotherapy treatment, and PB samples from healthy children, a robust evaluation of the immunological profile of Vδ1 and Vδ2 cells was performed by flow cytometry and different soluble immune mediators were measured through the Luminex platform. Our results demonstrated that patients with B-ALL, compared to the control group, presented a significant increase in Vδ2 cells expressing activation and cytotoxicity markers. The kinetic evaluation during chemotherapy demonstrated that this subset maintained a phenotype linked to cytotoxicity and not exhaustion. Furthermore, the expression of CD69 and NKG2D was enriched in γδ T cells from patients with low tumor burden and low risk, while patients that did not exhibit measurable residual disease (MRD) at D35 exhibited a higher frequency of CXCR3- CXCR4- Vδ1 cells in the BM. This is the first study describing the frequency and immunological profile of γδ T cells in patients with pediatric B-ALL.