Double negative T-cells in acute lymphoblastic leukemia: a pilot study in pediatric patients

Objective . Double negative T cells are involved in various neoplastic processes including hematologic malignancies such as acute lymphoblastic leukemia. These unconventional lymphocytes express neither CD4 nor CD8 and play a role in immune modulation in cancer, particularly in the bone marrow microenvironment. However, their specific involvement in acute lymphoblastic leukemia and other leukemias, especially in pediatric patients, remains poorly understood. The present pilot study aims to characterize double negative T-cells in children with acute lymphoblastic leukemia and compare them with healthy controls. Materials and methods. A prospective, cross-sectional study of 20 children diagnosed with acute lymphoblastic leukemia and 9 healthy, ageand sex-matched control participants was performed. Flow cytometry was used to evaluate lymphocyte subpopulations, including double negative T-cells. Results and Discussion . The total number of double negative T cells significantly increased in patients with acute lymphoblastic leukemia compared to controls. In particular, αβ+DNT cells were markedly increased in patients with acute lymphoblastic leukemia both in percentage and absolute values. At the same time, γδ+DNT cells were significantly decreased in patients with acute lymphoblastic leukemia in absolute number and in proportion to CD3+ lymphocytes. Conclusions . αβ+DNT cells are significantly elevated in children with acute lymphoblastic leukemia, suggesting their possible role in the immune response to leukemia. However, this increase may reflect a broader immune dysregulation rather than being specific to acute lymphoblastic leukemia. Further studies are required to clarify their role in leukemia and to explore their therapeutic potential.