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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 6/2011

01-12-2011

IL-9 Contributes to Immunosuppression Mediated by Regulatory T Cells and Mast Cells in B-Cell Non-Hodgkin’s Lymphoma

Authors: Li-Li Feng, Jun-Ming Gao, Pei-Pei Li, Xin Wang

Published in: Journal of Clinical Immunology | Issue 6/2011

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Abstract

It has been known that regulatory T (Treg) cells and mast cells (MCs) are involved in tumor immunity regulation, but the exact roles and mechanisms of Treg cells and MCs in B-cell non-Hodgkin’s lymphoma (NHL) are incompletely defined. In the present study, we found that the number of Foxp3+ Treg cells and CD117+ MCs increased in B-cell NHL patients. Concomitantly, a high level of interleukin (IL)-9 was observed in the sera from B-cell NHL patients. Neutralizing IL-9 significantly inhibited tumor growth in the lymphoma model of murine, and this process was associated with down-regulation of Treg cells and MCs. Furthermore, IL-9 was also demonstrated to induce expression of MC-related genes and proliferation of MCs from the bone marrow stem cells. Collectively, our results indicate that Treg cell and MCs are involved in immunosuppression in B-cell NHL, and IL-9 is a key mediator of Treg cells and MCs in that process. These findings provide novel insight for the pathogenesis and possible therapeutic strategy of B-cell NHL.
Literature
1.
Lippman SM, Spier CM, Miller TP, et al. Tumor-infiltrating T-lymphocytes in B-cell diffuse large cell lymphoma related to disease course. Mod Pathol. 1990;3(3):361–7.PubMed
2.
de Jong D. Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic factors. J Clin Oncol. 2005;23(26):6358–63.PubMedCrossRef
3.
Drach J, Seidl S, Kaufmann H. Treatment of mantle cell lymphoma: targeting the microenvironment. Expert Rev Anticancer Ther. 2005;5(3):477–85.PubMedCrossRef
4.
Ansell SM, Stenson M, Habermann TM, et al. CD4+ T-cell immune response to large B-cell non-Hodgkin’s lymphoma predicts patient outcome. J Clin Oncol. 2001;19(3):720–6.PubMed
5.
Lawrence T. Inflammation and cancer: a failure of resolution? Trends Pharmacol Sci. 2007;28(4):162–5.PubMedCrossRef
6.
Balkwill F, Charles KA, Mantovani A. Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 2005;7(3):211–7.PubMedCrossRef
7.
Zou W, Regulatory T. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6(4):295–307.PubMedCrossRef
8.
Ullrich SE, Nghiem DX, Khaskina P. Suppression of an established immune response by UVA—a critical role for mast cells. Photochem Photobiol. 2007;83(5):1095–100.PubMedCrossRef
9.
Woo EY, Chu CS, Goletz TJ, et al. Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res. 2001;61(12):4766–72.PubMed
10.
Liyanage UK, Moore TT, Joo HG, et al. Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol. 2002;169(5):2756–61.PubMed
11.
Curiel TJ, Coukos G, Zou L, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10(9):942–9.PubMedCrossRef
12.
Viguier M, Lemaitre F, Verola O, et al. Foxp3 expressing CD4+CD25(high) regulatory T cells are overrepresented in human metastatic melanoma lymph nodes and inhibit the function of infiltrating T cells. J Immunol. 2004;173(2):1444–53.PubMed
13.
Dudley ME, Wunderlich JR, Robbins PF, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850–4.PubMedCrossRef
14.
Beyer M, Kochanek M, Darabi K, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood. 2005;106(6):2018–25.PubMedCrossRef
15.
Rech AJ, Vonderheide RH. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann N Y Acad Sci. 2009;1174:99–106.PubMedCrossRef
16.
Ansell SM, Hurvitz SA, Koenig PA, et al. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2009;15(20):6446–53.PubMedCrossRef
17.
Cao Y, Zhao J, Yang Z et al. CD4+FOXP3+ regulatory T cell depletion by low-dose cyclophosphamide prevents recurrence in patients with large condylomata acuminata after laser therapy. Clin Immunol. 2010;136(1):21–9.
18.
Galli SJ, Kalesnikoff J, Grimbaldeston MA, et al. Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu Rev Immunol. 2005;23:749–86.PubMedCrossRef
19.
Galli SJ, Nakae S, Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol. 2005;6(2):135–42.PubMedCrossRef
20.
Galinsky DS, Nechushtan H. Mast cells and cancer—no longer just basic science. Crit Rev Oncol Hematol. 2008;68(2):115–30.PubMedCrossRef
21.
Taskinen M, Karjalainen-Lindsberg ML, Leppa S. Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP. Blood. 2008;111(9):4664–7.PubMedCrossRef
22.
Huang B, Lei Z, Zhang GM, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment. Blood. 2008;112(4):1269–79.PubMedCrossRef
23.
Yang Z, Zhang B, Li D et al. Mast cells mobilize myeloid-derived suppressor cells and Treg cells in tumor microenvironment via IL-17 pathway in murine hepatocarcinoma model. PLoS One. 2010;5(1):e8922.
24.
Townsend JM, Fallon GP, Matthews JD, et al. IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity. 2000;13(4):573–83.PubMedCrossRef
25.
Hauber HP, Bergeron C, Hamid Q. IL-9 in allergic inflammation. Int Arch Allergy Immunol. 2004;134(1):79–87.PubMedCrossRef
26.
Lu LF, Lind EF, Gondek DC, et al. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 2006;442(7106):997–1002.PubMedCrossRef
27.
Eller K, Wolf D, Huber JM, et al. IL-9 production by regulatory T cells recruits mast cells that are essential for regulatory T cell-induced immune suppression. J Immunol. 2011;186(1):83–91.PubMedCrossRef
28.
Houot R, Levy R. T-cell modulation combined with intratumoral CpG cures lymphoma in a mouse model without the need for chemotherapy. Blood. 2009;113(15):3546–52.PubMedCrossRef
29.
Naito S, von Eschenbach AC, Giavazzi R, et al. Growth and metastasis of tumor cells isolated from a human renal cell carcinoma implanted into different organs of nude mice. Cancer Res. 1986;46(8):4109–15.PubMed
30.
Feng L, Sun X, Csizmadia E et al. Vascular CD39/ENTPD1 directly promotes tumor cell growth by scavenging extracellular adenosine triphosphate. Neoplasia. 2010;13(3):206–16.
31.
Liu Y, Li N, You L, et al. HSP70 is associated with endothelial activation in placental vascular diseases. Mol Med. 2008;14(9–10):561–6.PubMed
32.
Pillai V, Ortega SB, Wang CK, et al. Transient regulatory T-cells: a state attained by all activated human T-cells. Clin Immunol. 2007;123(1):18–29.PubMedCrossRef
33.
Zhang X, Li M, Lian D, et al. Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection. Clin Immunol. 2008;127(3):313–21.PubMedCrossRef
34.
Gri G, Piconese S, Frossi B, et al. CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40–OX40L interaction. Immunity. 2008;29(5):771–81.PubMedCrossRef
35.
Qiao H, Andrade MV, Lisboa FA, et al. FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells. Blood. 2006;107(2):610–8.PubMedCrossRef
36.
Stassen M, Hultner L, Schmitt E. Classical and alternative pathways of mast cell activation. Crit Rev Immunol. 2002;22(2):115–40.PubMed
37.
Wu B, Huang C, Kato-Maeda M, et al. IL-9 is associated with an impaired Th1 immune response in patients with tuberculosis. Clin Immunol. 2008;126(2):202–10.PubMedCrossRef
38.
Renauld JC, Kermouni A, Vink A, et al. Interleukin-9 and its receptor: involvement in mast cell differentiation and T cell oncogenesis. J Leukoc Biol. 1995;57(3):353–60.PubMed
39.
Elyaman W, Bradshaw EM, Uyttenhove C, et al. IL-9 induces differentiation of TH17 cells and enhances function of FoxP3+ natural regulatory T cells. Proc Natl Acad Sci USA. 2009;106(31):12885–90.PubMedCrossRef
40.
Hu ZQ, Zhao WH, Shimamura T. Regulation of mast cell development by inflammatory factors. Curr Med Chem. 2007;14(28):3044–50.PubMedCrossRef
Metadata
Title
IL-9 Contributes to Immunosuppression Mediated by Regulatory T Cells and Mast Cells in B-Cell Non-Hodgkin’s Lymphoma
Authors
Li-Li Feng
Jun-Ming Gao
Pei-Pei Li
Xin Wang
Publication date
01-12-2011
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 6/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-011-9584-9

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