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Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy

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Abstract

Dendritic cells (DCs) are professional antigen-presenting cells to initiate immune responses, and DC survival time is important for affecting the strength of T-cell responses. Interleukin (IL)-9-producing T-helper (Th)-9 cells play an important role in anti-tumor immunity. However, it is unclear how Th9 cells communicate with DCs. In this study, we investigated whether murine Th9 cells affected the survival of myeloid DCs. DCs derived from bone marrow of C57BL/6 mice were cocultured with Th9 cells from OT-II mice using transwell, and the survival of DCs was examined. DCs cocultured with Th9 cells had longer survival and fewer apoptotic cells than DCs cultured alone in vitro. In melanoma B16-OVA tumor-bearing mice, DCs conditioned by Th9 cells lived longer and induced stronger anti-tumor response than control DCs did in vivo. Mechanistic studies revealed that IL-3 but not IL-9 secreted by Th9 cells was responsible for the prolonged survival of DCs. IL-3 upregulated the expression of anti-apoptotic protein Bcl-xL and activated p38, ERK and STAT5 signaling pathways in DCs. Taken together, our data provide the first evidence that Th9 cells can promote the survival of DCs through IL-3, and will be helpful for designing Th9 cell immunotherapy and more effective DC vaccine for human cancers.

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Abbreviations

Ab:

Antibody

BM:

Bone marrow

CFSE:

5(6)-Carboxyfluorescein diacetate succinimidyl ester

DC:

Dendritic cells

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

IFN-r :

Interferon gamma

IL:

Interleukin

OVA:

Ovalbumin

PMA:

Phorbol myristate acetate

Th:

T-helper

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

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Acknowledgments

This work was supported by grants from the National Cancer Institute (R01 CA96569, R01 CA103978, R01 CA138402 and P50 CA142509), the Leukemia & Lymphoma Society and Multiple Myeloma Research Foundation.

Conflict of interest

The authors declare no competing financial interests.

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Author notes

  1. Haiyan Li, Mingjun Zhang, Yong Lu, Bangxing Hong, Yuhuan Zheng, Jianfei Qian & Qing Yi

    Present address: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue/NB40, Cleveland, OH 44195, USA

Authors and Affiliations

  1. Department of Lymphoma and Myeloma, Division of Cancer Medicine, and Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Jungsun Park, Haiyan Li, Mingjun Zhang, Yong Lu, Bangxing Hong, Yuhuan Zheng, Jin He, Jing Yang, Jianfei Qian & Qing Yi

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  1. Jungsun Park
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Correspondence to Qing Yi.

Additional information

Jungsun Park and Haiyan Li have contributed equally to this work.

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Park, J., Li, H., Zhang, M. et al. Murine Th9 cells promote the survival of myeloid dendritic cells in cancer immunotherapy. Cancer Immunol Immunother 63, 835–845 (2014). https://doi.org/10.1007/s00262-014-1557-4

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