Th17 cells and interleukin‐17 increase with poor prognosis in patients with acute myeloid leukemia

Abstract

Although Th17 cells play crucial roles in the pathogenesis of many autoimmune and inflammatory disorders, their roles in malignancies are currently under debate. The role and mechanism of Th17 cells in patients with acute myeloid leukemia (AML) remain poorly understood. Here we demonstrated that the frequency of Th17 cells was significantly increased in peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells from AML patients compared with healthy donors. Plasma levels of interleukin (IL)-17, IL-22, IL-23, IL-1β, IL-6, and transforming growth factor (TGF)-β1 were significantly increased in blood and bone marrow in AML patients compared with healthy donors. The in vitro experiments demonstrated that IL-1β, IL-6, IL-23, but not TGF-β1 promoted the generation and differentiation of Th17 cells from naive CD4+ T cells in humans. IL-17A, a signature cytokine secreted by Th17 cells, induced the proliferation of IL-17 receptor (IL-17R)-positive AML cells via IL-17R, in which activation of PI3K/Akt and Jak/Stat3 signaling pathway may play important roles. In addition, combination of IL-17A and IL-22 significantly reduced the generation of Th1 cells and the production of interferon (IFN)-γ from healthy donor or AML patient peripheral blood mononuclear cells. Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival. Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes. In conclusion, Th17 cells play a crucial role in the pathogenesis of AML and may be an important therapeutic target and prognostic predictor.

Interleukin-6 levels predict event-free survival in pediatric AML and suggest a mechanism of chemotherapy resistance

“…In contrast to results adult AML, 10,11 IL-8 and IL-10 levels were not correlated with EFS ( Figure 2D-E).…”

“…These data are similar to several previous studies that showed elevated levels in peripheral blood and BM of IL-6, IL-10, IL-8, IL-4, TNF-a, and IL-17A in adult patients with AML. 10,11 Among the various cytokines tested, only elevated IL-6 levels predicted lower survival in our cohort. The significance of this relationship was emphasized when data were limited to patients classified as LR by current criteria.…”

“…10 Additionally, elevated levels of some cytokines in the adult AML bone marrow (BM) niche have been described, including IL-6. 11 Recently, a study of a small pediatric AML cohort showed that IL-6 levels in peripheral blood were elevated compared with healthy age-matched controls. 12 However, the cytokine milieu in the BM niche of pediatric patients with AML has not been investigated previously.…”

Differential Adverse Events Between TNF-α Inhibitors and IL-17 Axis Inhibitors for the Treatment of Spondyloarthritis

“…Similarly, several cases of grade 1 leukopenia and neutropenia were reported in AS patients receiving secukinumab, but the exact number of cases was not noted [48]. Recent studies have established an important role of Th17 cells, the manufacturers of IL-17, in the pathogenesis of acute myeloid leukemia [57,58]; it is possible that when a mechanism along these lines is blocked, such cytopenias are resultant.…”

Emerging Cytokine Networks in Osteosarcoma

“…Although its role in tumorigenesis is still controversial [85,86] , the presence of IL-17 has been verified and associated with poor prognosis in different types of cancers [87,88] .…”