Leukemic susceptibility mediated by functional ligands of natural killer cells

• Grant number: 24/02164-5
• Support Opportunities: Regular Research Grants
• Duration: July 01, 2024 - June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Convênio/Acordo: CNPq
• Principal Investigator: Lorena Lôbo de Figueiredo Pontes
• Grantee: Lorena Lôbo de Figueiredo Pontes
• Host Institution: Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil
• Associated research grant: 21/06841-3 - Molecular and phenotypical mechanisms driving immune evasion in myeloid malignancies, AP.JP2
• Associated scholarship(s): 24/13669-0 - Leukemic susceptibility mediated by functional ligands of natural killer cells, BP.JD

Abstract

Despite advances in the diagnosis and treatment of acute myeloid leukemia (AML), the cure rate remains low even in patients with so-called favorable genetic characteristics and therapies that rarely include targeted drugs and bone marrow transplantation. Monitoring therapy response through measurable residual disease research helps predict outcomes, although clinical management for persistent disease is still not well established. In this context, antitumor immunosurveillance may contribute to the elimination of residual leukemic cells. Studies from this research group demonstrate interference in tumor recognition and reduced cytotoxicity in myeloid neoplasm models mediated by an imbalance of Natural Killer (NK) cell receptors, favoring leukemogenesis. However, the role of interaction between ligands expressed on leukemic stem cells and NK receptors in antitumor resistance is not fully understood. We believe that modulation of NK activation and inhibition ligands on leukemic cells may reverse immune tolerance. Thus, we aim to clarify the role of NK ligands in leukemia persistence, characterizing them immunophenotypically and functionally in murine models and primary AML cells of different genetic subtypes and clinical outcomes. Moreover, reversal of resistance phenotype will be evaluated through inhibition/superexpression assays of NK ligands in leukemic progenitor cells. (AU)