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Hepatic myeloid-derived suppressor cells in cancer

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Abstract

Myeloid-derived suppressor cells are key components of tumor-induced immune suppression. They are composed of a heterogeneous population of immature myeloid cells that abrogates innate and adaptive immune responses. Myeloid-derived suppressor cells accumulate not only in peripheral blood, secondary lymphoid organs and tumors, but also in the liver in preclinical tumor models and in hepatocellular carcinoma patients. The liver, continuously exposed to food and microbial antigens from the intestine, avoids autoimmune damage through the use of specialized mechanisms of immune tolerance. In the context of cancer, myeloid-derived suppressor cells profit the intrinsic tolerogenic properties of the liver to accumulate and exert various immune-suppressive and tumor-promoting mechanisms which go from inducing immune cell dysfunction to supporting the generation of liver metastases. In this review, we seek to describe the phenotype, function, accumulation and therapeutic targeting of hepatic myeloid-derived suppressor cells both in preclinical settings and in the context of human hepatocellular carcinoma.

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Abbreviations

ADCC:

Antibody-dependent cell cytotoxicity

CAR:

Chimeric antigen receptor

DC:

Dendritic cell

HCC:

Hepatocellular carcinoma

H2O2 :

Hydrogen peroxide

IFN-γ:

Interferon gamma

iNOS:

Inducible nitric oxide synthase

MDSC:

Myeloid-derived suppressor cell

MHC-II:

Major histocompatibility complex-II

mTOR:

Mammalian target of rapamycin

NOX2:

NADPH oxidase 2

NK:

Natural killer

NO:

Nitric oxide

OVA:

Ovalbumin

PBMC:

Peripheral blood mononuclear cell

PD-L1:

Programmed death ligand 1

PNT:

Peroxynitrite

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

Treg :

Regulatory T cell

TGF-β1:

Transforming growth factor beta 1

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Acknowledgments

We especially thank Joselyn Natasha Allen for artwork design and the NIH Fellows Editorial Board for editorial assistance. This work was supported by the Intramural Research Program of the National Cancer Institute, NIH.

Conflict of interest

The authors declare no commercial or financial conflict of interest.

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Authors and Affiliations

  1. Gastrointestinal Malignancy Section, Thoracic and Gastrointestinal Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, NIH/NCI/CCR Building 10, Rm 12N226, 9000 Rockville Pike, Bethesda, MD, 20892, USA

    José Medina-Echeverz, Tobias Eggert, Miaojun Han & Tim F. Greten

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  1. José Medina-Echeverz
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  2. Tobias Eggert
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Correspondence to Tim F. Greten.

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Medina-Echeverz, J., Eggert, T., Han, M. et al. Hepatic myeloid-derived suppressor cells in cancer. Cancer Immunol Immunother 64, 931–940 (2015). https://doi.org/10.1007/s00262-015-1736-y

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