Prognostic value of Th17 cells in acute leukemia

Abstract

Th17 cells and their effector cytokines have emerged as important mediators in inflammatory and autoimmune diseases and serve as an ambitious field in current immunology research. Recent studies suggest a potential impact of Th17 cells on solid tumors but relatively little is known about their contribution in hematological malignancies. The current study was designed to investigate the possible involvement and clinical significance of circulating Th17 cells in acute leukemia. Flow cytometry was used to analyze percentages of Th17 cells in peripheral blood mononuclear cells from 93 acute leukemia patients (ALL, n = 30; AML, n = 63) and 40 healthy volunteers. Serum levels of IL-17 and IL-21 were measured using enzyme-linked immunosorbent assay. Circulating Th17 cells were increased in patients with acute leukemia (2.88 ± 0.65 % and 2.90 ± 0.57 % in ALL and AML patients, respectively) and were significantly higher than in healthy controls (1.10 ± 0.28 %; P = 0.001). Furthermore, pretreatment Th17 cells were reduced significantly in patients who achieved complete remission after induction therapy (2.25 ± 0.44 % and 1.63 ± 0.27 % in ALL and AML patients, respectively, P < 0.0001). Serum levels of IL-17 and IL-21 were significantly elevated in acute leukemia patients. Kaplan–Meier curves revealed a significantly longer overall survival in patients with high Th17 levels (P = 0.029 and P = 0.027 for ALL and AML, respectively). In the multivariate analysis, Th17 cells retained statistical significance for overall survival in patients with ALL (OR 0.331; P = 0.043) and AML (OR 0.489; P = 0.032). These results strongly suggest Th17 cells as a powerful new prognostic determinant which could serve as a potential therapeutic target to modulate anti-tumor response in acute leukemia patients.

The correlations between IL-17 vs. Th17 cells and cancer patient survival: a systematic review

“…15,16,[18][19][20][24][25][26][40][41][42][43][44][45][46] Leukemia on the other hand might provide an environment favorable for Th17 cells to suppress tumor growth. 32,38 Similarly, ovarian cancer might attract a tumor suppressing IL-17 response, as the majority of studies found a correlation with a favorable outcome. 28,69 A possible explanation might be that different microenvironments favor infiltration of or differentiation toward more or less tumor-promoting immune cell phenotypes.…”

“…17,[24][25][26]31 One study showed a correlation between high IL-17 and improved survival in leukemia. 32 Four studies did not observe a significant correlation between high serum IL-17 levels and survival, [33][34][35][36] although one group did find a trend toward poor prognosis (p D 0.05). 36 Overall, a high amount of IL-17 protein in serum has predominantly been correlated with poor survival ( Table 2).…”

IL - 17 Assay in Adult T-Cell Leukemia - Lymphoma Patients with Dermatophytosis

“…On the other hand our findings were more or less similar to that detected by T Miyagaki,et al 19 who reported that IL-17A not significantly elevated in lesional skin of cutaneous T-cell lymphoma. Also a recent study carried out in Oncology Center, Mansoura University reported that serum levels of IL-17 and IL-21 in untreated acute leukemia patients were significantly higher than in controls and correlated positively with levels of circulating Th17 cells 20 .…”

Prognostic significances of interleukin-17-producing cells and Th17 cells in malignant cancers: a meta-analysis of the literatures

“…The level of Th17 cells in peripheral blood of cancer patients is frequently founded to be higher than that in normal control, which might suggest an underlying inflammatory status [35]. Interesting, the high Th17 cells sampled from peripheral blood of patients with leukemia was correlated with better survival [67,68], while high Th17 cells sampled from bone marrow of patients with leukemia was an indicator of worse survival [69].…”

“…Finally, we also investigated the impact of Th17 cells on OS in 10 studies with 727 patients (Fig 4.C) [18,19,56,[63][64][65][66][67][68][69]. The Th17 cells were identified by flow cytometery analysis in all included studies.…”