Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells

Abstract

Th17 cells are a newly found subset of distinct CD4+ Th effector cells' family and are found to play an important role in cancers. Myelodysplastic syndromes (MDS) are a common malignant hematological disease. Here, we showed that both the percentage and the function of Th17 cells were elevated in low-risk MDS while being decreased in high-risk MDS. Levels of upstream molecules of Th17 cells, IL-6 and IL-23, were higher in low-risk MDS but lower in high-risk MDS patients. The abnormal percentage of Th17 cells was closely related to clinical parameters including karyotype, morphologic blast percentage of bone marrow, peripheral absolute neutrophil count, and hemoglobin concentration. Furthermore, expression rates of perforin and granzyme B in BM CD3+CD8+ cells (cytotoxic T lymphocyte, CTL) positively correlated with levels of IL-17 but negatively correlated with BM blast percentage and could be significantly increased after stimulation with human recombinant IL-17 (rhIL-17). Our results suggested that Th17 cells might play an antitumor effect in the pathogenesis of MDS through IL-17/CTL pathway.

The cryo-thermal therapy-induced IL-6-rich acute pro-inflammatory response promoted DCs phenotypic maturation as the prerequisite to CD4+T cell differentiation

“…No significant changes were found in Tfh related genes among the cryo-thermal therapy, IL-6 neutralisation and control group (Figure 5(E)). These data suggested that acute IL-6 at the early stage induced by the cryo-thermal therapy would promote CD4 þ T cells differentiation into CTL, Th1, and especially Th17 [47,48].…”

“…Mice spleen were then harvested for preparation of single cell suspension. (A&B&C).Flow-cytometry analysis of the dynamic change of mature DCs (CD11c þ CD86 þ MHCII þ ) was performed at different time points after the treatment(24,48,72 and 120 h after the treatment), compared with the tumour-bearing control group. n ¼ 4 mice at each time point per group.…”

Expression of IL-23/Th17-related cytokines in basal cell carcinoma and in the response to medical treatments

“…Induction of angiogenesis and of tumor-promoting cytokines, as IL-6 and IL-8, might explain the pro-tumoral effect [ 49 ]. On the other hand, evidences for the tumor suppressive function of the IL-23/Th17 axis have been described in B-acute lymphoblastic leukemia [ 19 ], myelodysplastic syndromes [ 50 ], hepatocellular carcinoma [ 51 ], in ovarian [ 52 ] and prostate [ 53 ] cancers. The anti-tumor effects seem to be mediated by multiple pathways, including inhibition of T regs, induction of cytotoxic activity and the synergic action with Th1 response [ 15 ].…”

The inflammatory cytokine profile of myelodysplastic syndromes

“…However, the results remained controversial. The study conducted by Li et al [9] showed that when considered as a whole group, the levels of IL-17 and IL-6 in MDS patients did not elevate comparing with healthy controls. The research of Shao et al [10] indicated that both in peripheral blood and bone marrow samples, the levels of IL-17 has no significant difference between MDS patients and healthy controls either.…”