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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Blocking / administration & dosage
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B-Lymphocytes / pathology
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Bone Marrow / pathology
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Cells, Cultured
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Forkhead Transcription Factors / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Immunosuppression Therapy
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Interleukin-9 / biosynthesis*
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Interleukin-9 / blood
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Interleukin-9 / genetics
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Interleukin-9 / immunology
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Lymphoma, Non-Hodgkin / blood
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Lymphoma, Non-Hodgkin / drug therapy
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Lymphoma, Non-Hodgkin / immunology*
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Lymphoma, Non-Hodgkin / pathology
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Mast Cells / drug effects
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Mast Cells / immunology
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Mast Cells / metabolism*
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Mast Cells / pathology
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Mice
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Mice, Inbred BALB C
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Neoplasm Transplantation
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Proto-Oncogene Proteins c-kit / metabolism
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T-Lymphocytes, Regulatory / drug effects
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / pathology
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Tumor Burden / drug effects
Substances
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Antibodies, Blocking
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FOXP3 protein, human
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Forkhead Transcription Factors
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Interleukin-9
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Proto-Oncogene Proteins c-kit