IL-8 in bone marrow and peripheral blood of patients with B-cell acute lymphoblastic leukemia is associated with high regulatory T cell counts, degree of tumor infiltration and expression of CXCR1 in blasts

Abstract

Introduction: Regulatory T cells (Treg cells) in a tumor environment and the expression of forkhead box P3 (FOXP3) in tumor cells have been associated with a poor prognosis. There are few studies evaluating Treg cells and FOXP3 in B-cell acute lymphoblastic leukemia (B-cell ALL). This study aimed to evaluate the frequencies of Treg cells in bone marrow (BM) and peripheral blood (PB) of patients with B-cell ALL and to determine their associations with the circulating cytokine profile and the expression of CXCR1 (IL-8 receptor) in Treg cells, as well as to compare FOXP3 expression in blasts of patients with B-cell ALL and normal lymphoid precursors. Methods: Samples of BM and PB from patients with B-cell ALL and healthy controls were studied. Treg cells, cytokines, FOXP3 and CXCR1 were evaluated using flow cytometry and analyzed. Results: A total of 20 patients with B-cell ALL and 10 healthy controls were included. In B-cell ALL patients, Treg cell frequencies increased significantly, with higher percentages in the PB. Absolute Treg cell counts were associated with absolute blast counts in the BM and PB and with an IL-8 concentration. The IL-8 and IL-6 levels were associated with the CXCR1 expression in PB Treg cells. In addition, a greater expression of FOXP3 was observed in leukemic blasts than in normal lymphoid precursors. Conclusions: These results suggest that the presence of Treg cells and cytokines in the tumor environment may correspond to mechanisms to evade the immune response. For that reason, it would be important to monitor these parameters in B-cell ALL to establish their effect on the disease prognosis.

Keywords

• Regulatory T cells
• B-cell acute lymphoblastic leukemia
• IL-8
• Cytokines
• Flow cytometry