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

Journal of Immunology Research, Sep 2016

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

Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8+ T Cells Jing Li, Lanzhu Yue, Huaquan Wang, Chunyan Liu, Hui Liu, Jinglian Tao, Weiwei Qi, Yihao Wang, Wei Zhang, Rong Fu, and Zonghong Shao Department of Hematology, The General Hospital of Tianjin Medical University, Tianjin, China Received 15 April 2016; Accepted 27 June 2016 Academic Editor: Dipayan Rudra Copyright © 2016 Jing Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduction Myelodysplastic syndromes (MDS) are a diverse group of clonal hematopoietic malignancies characterized by ineffective hematopoiesis, progressive bone marrow failure, cytogenetic and molecular abnormalities, and unpredictable risk of further deteriorating into acute myeloid leukemia (AML) [1]. Pathogenesis of MDS is complicated and sustained by a burden of recurrent molecular, cytogenetic, and epigenetic defects. Numerous clinical and experimental data suggest the involvement of T lymphocytes in the pathogenesis of MDS; however the actual weight exerted by T cells in this scenario is yet to be conclusively dissected [2]. Previous studies from our group and others found that the number of Th1 cells was decreased with Th2 cells increasing relatively resulting in an imbalance of Th1/Th2, which was proved to be correlated with condition of MDS patients [3]. What is more, the frequency of Treg cells was elevated with hyperfunction and was obviously correlated with the disease condition of MDS patients [4–6]. Patients with high-risk MDS also had higher frequency of T regulatory cells than normal [7], which suggested that progression of MDS was facilitated by immune suppression and tumor immune deficiency. Lately even Th17 cells have been advocated in the pathogenesis of MDS for the first time [8]. Th17 cells, named by their signature cytokine IL-17, are a distinct subset of CD4+ Th effector cells with RAR-related orphan receptor γt (RORγt) and signal transducers and activators of transcription-3 (STAT-3) as the transcription factor to direct their differentiation. Many researches have clarified the importance of Th17 cells in inducing inflammation and autoimmune tissue injury to defend against microbial infections. However, the role of Th17 cells acting in the pathogenesis of malignant diseases remains equivocal as the available data showed a contribution of Th17 cells to either protective antitumor immunity or promoting tumor growth by IL-17 and IL-23 [9, 10]. Although more and more results have supported the antitumor effects of Th17 cells by eradicating tumor cells directly or recruiting other tumor-specific immune cells and/or by promoting their antitumor immune responses [11], most data are derived from murine models; the role and pathway of human Th17 cells in antitumor immunity are still incompletely defined. Our present study seeks to illuminate roles of Th17 cells in the pathogenesis of MDS patients in different risk groups through measuring the frequency of Th17 cells, detecting levels of related cytokines in patients with different risks of MDS, analyzing the correlation between Th17 cells percentage and hematological parameters of MDS patients, and testing levels of cytotoxic molecules expressed in CTL before and after human recombinant IL-17 (rhIL-17) stimulation, ultimately to explore the role of Th17 cells in the tumorigenesis of MDS. 2. Materials and Methods2.1. Study Populations A total of 42 patients (18 females and 24 males; range from 21 to 84; median age 58 years) with MDS were enrolled in this study. Patients were treatment-naive when sampling. All were inpatients of the Hematology Department of General Hospital Tianjin Medical Univers (...truncated)


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Jing Li, Lanzhu Yue, Huaquan Wang, Chunyan Liu, Hui Liu, Jinglian Tao, Weiwei Qi, Yihao Wang, Wei Zhang, Rong Fu, Zonghong Shao. Th17 Cells Exhibit Antitumor Effects in MDS Possibly through Augmenting Functions of CD8, Journal of Immunology Research, 2016, 2016, DOI: 10.1155/2016/9404705