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Signal transducer and activator of transcription proteins: regulators of myeloid-derived suppressor cell-mediated immunosuppression in cancer

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Abstract

The success of cancer immunotherapy in patients depends on overcoming immunosuppressive mechanisms in addition to stimulating effective anticancer immune responses. Myeloid-derived suppressor cells (MDSCs) inhibit a spectrum of immune responses, including adaptive immune responses and innate immune responses at the tumor site. MDSCs have been targeted to overcome immunosuppression either by reducing their numbers or downregulating their immunosuppressive activities. Although signal transducer and activator of transcription (STAT) proteins are recognized as signaling and transcription factors induced by cytokines in normal cells, they also have roles in cancer and cancer-related cells, as well as MDSC differentiation and function. In in vitro and in vivo studies, including studies on humans, selective STAT3 inhibitors such as Stattic and S3I-201 have demonstrated potential in regulating MDSC-mediated immunosuppression. Thus, STAT pathways represent a promising target in cancer immunotherapy. Herein, we review the roles of STAT signaling in MDSC biology, and the clinical potential of STAT inhibitors in regulating tumor-associated immunosuppression mediated by MDSCs.

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Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean government (Ministry of Science, ICT & Future Planning) (NRF-2013R1A1A3011482).

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  1. Laboratory of Microbiology and Immunology, College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea

    Hyun-Jeong Ko

  2. Laboratory of Microbiology and Immunology, College of Pharmacy, Inje University, Gimhae, 621-749, Republic of Korea

    Yeon-Jeong Kim

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Correspondence to Yeon-Jeong Kim.

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Ko, HJ., Kim, YJ. Signal transducer and activator of transcription proteins: regulators of myeloid-derived suppressor cell-mediated immunosuppression in cancer. Arch. Pharm. Res. 39, 1597–1608 (2016). https://doi.org/10.1007/s12272-016-0822-9

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