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Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model

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Abstract

The objective of this study was to investigate the immunomodulatory effect of cisplatin (DDP) on the frequency, phenotype and function of myeloid-derived suppressor cells (MDSC) in a murine B16 melanoma model. C57BL/6 mice were inoculated with B16 cells to establish the murine melanoma model and randomly received treatment with different doses of DDP. The percentages and phenotype of MDSC after DDP treatment were detected by flow cytometry. The immunoinhibitory function of MDSC was analyzed by assessing the immune responses of cocultured effector cells through CFSE-labeling assay, detection of interferon-γ production and MTT cytotoxic assay, respectively. Tumor growth and mice survival were monitored to evaluate the antitumor effect of combined DDP and adoptive cytokine-induced killer (CIK) cell therapy. DDP treatment selectively decreased the percentages, modulated the surface molecules and attenuated the immunoinhibitory effects of MDSC in murine melanoma model. The combination of DDP treatment and CIK therapy exerted synergistic antitumor effect against B16 melanoma. DDP treatment selectively downregulated the frequency and immunoinhibitory function of MDSC in B16 melanoma model, indicating the potential mechanisms mediating its immunomodulatory effect.

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Abbreviations

ATRA:

All-trans-retinoic acid

CFSE:

Carboxyfluorescein succinimidyl ester

CIK:

Cell cytokine-induced killer cell

DC:

Dendritic cells

DDP:

Cisplatin

IFN-γ:

Interferon-γ

IL-2:

Interleukin-2

i.p.:

Intraperitoneally

i.v.:

Intravenously

MDSC:

Myeloid-derived suppressor cells

MFI:

Mean fluorescence index

MHC:

Major histocompatibility complex

MTT:

Methyl thiazolyl tetrazolium

NS:

Normal saline

PB:

Peripheral blood

TDLN:

Tumor-draining lymph node

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Acknowledgments

This study was supported by a grant from the National Natural Science Foundation of China (NSFC 81201597) to Xiang Huang and grant from the National Natural Science Foundation of China (NSFC 81502611) to Shiyun Cui.

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    Authors and Affiliations

    1. Department of Medical Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, China

      Xiang Huang, Shiyun Cui & Yongqian Shu

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    1. Xiang Huang
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    2. Shiyun Cui
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    3. Yongqian Shu
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    Correspondence to Yongqian Shu.

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    Xiang Huang and Shiyun Cui have contributed equally to this work.

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    Huang, X., Cui, S. & Shu, Y. Cisplatin selectively downregulated the frequency and immunoinhibitory function of myeloid-derived suppressor cells in a murine B16 melanoma model. Immunol Res 64, 160–170 (2016). https://doi.org/10.1007/s12026-015-8734-1

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