Regulatory T cells-derived IL-35 promotes the growth of adult acute myeloid leukemia blasts

Abstract

Tumor immune escape mechanism mediated by CD4+CD25+regulatory T cells (Tregs) is a key factor in the pathogenesis of acute myeloid leukemia (AML). IL-35, as a novel inhibitory cytokine, is produced by Tregs specially and regulates functions of Tregs in murine. However, IL-35 expression of Tregs in human is still disputed, and its role in AML is yet to be elucidated. In this study, we found that IL-35 was expressed highly in peripheral blood plasma of adult patients with AML and significantly correlated with the clinical stages of malignancy. Tregs-derived from adult AML patients produced IL-35 in a stimulation-dependent manner. IL-35 promoted AML blasts immune escape by expanding Tregs and inhibiting CD4+CD25-effector T cells (Teffs). Furthermore, IL-35 directly promoted the proliferation of AML blasts and reduced the apoptosis of AML blasts. Together, our study demonstrates that IL-35-derived from Tregs promotes the growth of adult AML blasts, suggesting that IL-35 has an important role in the pathogenesis of AML. What's new? The inhibitory cytokine IL-35 is produced by regulatory T-cells (Tregs) in mice, where it is involved in the suppression of inflammation and tumorigenic processes. By comparison, much less is known about IL-35 expression and function in humans. Here, in adult patients with acute myeloid leukemia (AML), a disease influenced by Treg-mediated immune escape, human Tregs were discovered to produce IL-35 in a stimulation-dependent manner. IL-35 production facilitated the immune escape of adult AML blasts, promoted blast growth, and reduced blast apoptosis. IL-35 may be a key therapeutic target in adult AML.