Increased population of CD4<sup>+</sup>CD25<sup>high</sup> regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

Wang, Xingbing; Zheng, Jianming; Liu, Jun; Yao, Junxia; He, Yanli; Li, Xiaoqing; Yu, Jianpeng; Yang, Jinqiang; Liu, Zhongping; Huang, Shiang

doi:10.1111/j.1600-0609.2005.00537.x

Cited by 126 publications

(93 citation statements)

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“…Analogous to our findings in E-MDS patients, T reg deficiency has also been reported in idiopathic aplastic anemia, 48 further supporting a shared and overlapping pathogenesis between the two disorders. In addition, as in L-MDS, an expansion of functionally normal T regs is observed in patients with acute leukemia, 35 providing further evidence for a link between T reg -mediated immunomodulation and malignant hematopoiesis. Given the effectiveness of immunosuppressive regimens in MDS and the encouraging results of the T reg immunotherapy in solid neoplasms and autoimmune conditions, 49,50 our findings set the scene for the incorporation of the therapeutic manipulation of T regs in MDS.…”

Section: Discussionmentioning

confidence: 94%

“…These results are in line with numerous reports showing a marked increase of T regs in various solid and hematological malignancies. 22,[33][34][35][36][37][38] Even though still poorly understood, it T reg kinetics, function and trafficking in MDS I Kotsianidis et al seems that this expansion may be tumor-associated antigen (TAA) driven, as T reg clones can be generated by tumorassociated antigens and tumor-specific T regs can efficiently suppress TAA-specific immune responses. 39,40 The dramatic decline in T regs after tumor load reduction in high-risk MDS patients as well as their re-elevation, when these patients relapsed, further argues for tumor antigen-specific expansion of T regs in advanced stages of MDS.…”

Section: Discussionmentioning

confidence: 99%

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Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

et al. 2008

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CD4 þ CD25 þ FOXP3 þ T regulatory cells (T regs ) prevent autoimmunity by restricting overexuberant immune responses, but the same subpopulation can incur detrimental effects on antitumor responses. In both cases, the suppressor potential of T regs appears to be strongly influenced by their compartmentalization. In myelodysplastic syndromes (MDS), immune deregulation and autoimmunity in the early stages might lead to ineffective hematopoiesis and bone marrow (BM) failure, whereas late-stage disease is characterized by the immune escape of the malignant clone. We show that these two stages of MDS are associated with differential T reg activity. Specifically, we found that in early stage MDS, compared with normal hematopoiesis and late stage MDS, T regs are dysfunctional and their BM homing through the CXCL12/CXCR4 axis is seriously impaired as a result of CXCR4 downregulation. Conversely, in late stage MDS, T regs are systemically and locally expanded and retain their function and migratory capacity. Moreover, T reg levels follow the disease course and are significantly reduced in treatment responding patients. Our findings indicate T reg involvement in the pathophysiology of MDS; defective suppressor function and BM trafficking of T regs may be important in the autoimmune process of early MDS, but increased T reg activity could favor leukemic clone progression in late stage disease.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

et al. 2008

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“…62 Further on the level of T cells, several studies reported greater numbers of regulatory T cells (Treg) in AML patients compared to healthy donors. [63][64][65] Moreover, Treg frequencies were found to be lower when patients were in complete remission and higher when they relapsed. 65 Aside from an increased number, Treg of AML patients also demonstrated more potent suppression of responder T cells, mediated both via cell-to-cell contact as well as soluble factors such as IL-10 and transforming growth factor (TGF)-b1.…”

Section: How Aml Evades Nk Cell Immune Surveillancementioning

confidence: 96%

Natural killer cell immune escape in acute myeloid leukemia

et al. 2012

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“…However, little is known about the pathogenic events leading to the initiation and progression of this disease. Previously, elevated levels of regulatory T (Treg) cells in a variety of hematological malignancies including AML have been reported (5)(6)(7)(8). Patients with a lower Treg cell frequency at diagnosis have a better response to induction chemotherapy and a favorable prognosis (6,8).…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia

Shao

et al. 2012

Oncology Letters

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Abstract. Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and the development of myeloid cells and their precursors in the blood and bone marrow. Interleukin 35 (IL-35), a novel inhibitory cytokine secreted by regulatory T (Treg) cells is a novel potential target used for the therapeutic manipulation of Treg activity in order to treat cancer and autoimmune diseases. To investigate the role and imbalance of Treg-related cytokines in the pathogenesis of AML, we measured the plasma concentration of three Treg-associated cytokines [IL-35, IL-10 and transforming growth factor-β (TGF-β)] and evaluated their clinical relevance. The concentration of IL-35, IL-10 and TGF-β in plasma specimens from 55 patients with AML [27 newly diagnosed (ND) patients and 28 in complete remission (CR)] and 24 controls was analyzed using the enzyme-linked immunosorbent assay method. Significantly higher levels of plasma IL-35 and IL-10 were observed in AML ND patients compared with healthy controls or AML CR patients. IL-10 concentrations were positively correlated with TGF-β, whereas no correlations were found between the other cytokines. IL-10 levels were positively correlated with white blood cell (WBC) and neutrophil (NEU) count but there were no correlations between IL-35 and TGF-β with WBC and NEU count. In conclusion, we demonstrated for the first time that AML ND patients have increased plasma concentrations of IL-35, suggesting that this cytokine is involved in the pathophysiological process of the disease, and that further research is required to address this issue. IntroductionAcute myeloid leukemia (AML) is a life-threatening hematopoietic stem cell neoplasm characterized by an increase in the number of myeloid cells in the bone marrow and an arrest in their maturation, frequently resulting in fatal infection, bleeding or organ infiltration, with or without leukocytosis (1-3). The etiology of AML is heterogeneous and complex, but it is widely accepted that both environmental and genetic factors play significant roles in the development of the disease. Immune system disorders have increased our understanding of leukemogenesis (4). However, little is known about the pathogenic events leading to the initiation and progression of this disease. Previously, elevated levels of regulatory T (Treg) cells in a variety of hematological malignancies including AML have been reported (5-8). Patients with a lower Treg cell frequency at diagnosis have a better response to induction chemotherapy and a favorable prognosis (6,8).Treg + Treg cells, which are present in the normal immune system, engage in the maintenance of natural self-tolerance and also the control of immune responses to foreign antigens (9).IL-35, a member of the IL-12 family, is a recently identified heterodimeric cytokine consisting of Epstein-Barr virusinduced gene protein 3 (EBI3) and the p35 subunit of . In contrast to all other known IL-12 family members, which are not expressed by T cells, IL-35...

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Increased population of CD4⁺CD25^high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

Abstract: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.

Cited by 126 publications

References 32 publications

Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

Natural killer cell immune escape in acute myeloid leukemia

Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia

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Increased population of CD4+CD25high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients

Abstract: The frequency of CD4(+)CD25(high) T-reg in peripheral blood in AML patients is significantly higher when compared with healthy individuals, likely due to the increasing proliferation of CD4(+)CD25(high) T cells.

Cited by 126 publications

References 32 publications

Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS)

Natural killer cell immune escape in acute myeloid leukemia

Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia

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Increased population of CD4⁺CD25^high regulatory T cells with their higher apoptotic and proliferating status in peripheral blood of acute myeloid leukemia patients