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Immunomodulation by Schwann cells in disease

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Schwann cells are the principal glial cells of the peripheral nervous system which maintain neuronal homeostasis. Schwann cells support peripheral nerve functions and play a critical role in many pathological processes including injury-induced nerve repair, neurodegenerative diseases, infections, neuropathic pain and cancer. Schwann cells are implicated in a wide range of diseases due, in part, to their ability to interact and modulate immune cells. We discuss the accumulating examples of how Schwann cell regulation of the immune system initiates and facilitates the progression of various diseases. Furthermore, we highlight how Schwann cells may orchestrate an immunosuppressive tumor microenvironment by polarizing and modulating the activity of the dendritic cells.

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Abbreviations

ADORA1:

Adenosine A1 receptor

CCL:

C–C motif chemokine ligand

CIDP:

Chronic inflammatory demyelinating polyneuropathy

CXCL:

C–X–C motif chemokine ligand

DC:

Dendritic cell

EAN:

Experimental allergic neuritis

ECM:

Extracellular matrix

Gas6:

Growth arrest-specific protein 6

GBS:

Guillain–Barre syndrome

LFA:

Lymphocyte function-associated antigen

LIF:

Leukemia inhibitory factor

LPC:

Lysophosphatidylcholine

MBP:

Myelin basic protein

MCP-1:

Monocyte chemoattractant protein-1

MDSC:

Myeloid-derived suppressor cell

MIP:

Macrophage inflammatory protein

Nox1:

NADPH oxidase 1

P0:

Myelin protein zero

P2RX:

P2X purinoceptor

PLA2 :

Phospholipase A2

PMP-22:

Peripheral myelin protein 22

PNI:

Perineural invasion

PNS:

Peripheral nervous system

RAGE:

Receptor for advanced glycation end products

SAPP:

Spontaneous autoimmune peripheral polyneuropathy

SC:

Schwann cell

TµE:

Tumor microenvironment

TRPA1:

Transient receptor potential ankyrin 1

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Funding

The research was supported by the Research Scholar Grant, RSG-19-088-01-CSM (to Y. L. Bunimovich), from the American Cancer Society, and the Hillman Fellows for Innovative Cancer Research Program funded by the Henry L. Hillman Foundation (to Y. L. Bunimovich).

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Authors and Affiliations

  1. School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Sophia H. Zhang

  2. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Galina V. Shurin & Michael R. Shurin

  3. Department of Dermatology, University of Pittsburgh Medical Center, E1157 Thomas E. Starzl Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15213, USA

    Hasan Khosravi, Rashek Kazi, Oleg Kruglov & Yuri L. Bunimovich

  4. Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Michael R. Shurin

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  1. Sophia H. Zhang
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  2. Galina V. Shurin
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  3. Hasan Khosravi
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  4. Rashek Kazi
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  5. Oleg Kruglov
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  6. Michael R. Shurin
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  7. Yuri L. Bunimovich
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Contributions

Designed the study: MRS, YLB. Conducted experiments: GVS, OK, YLB. Wrote the manuscript: SHZ, HK, RK, MRS, YLB.

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Correspondence to Yuri L. Bunimovich.

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This paper is a Focussed Research Review based on a presentation given at the Sixth International Conference on Cancer Immunotherapy and Immunomonitoring (CITIM 2019), held in Tbilisi, Georgia, 29th April–2nd May 2019. It is part of a series of CITIM 2019 papers in Cancer Immunology, Immunotherapy.

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Zhang, S.H., Shurin, G.V., Khosravi, H. et al. Immunomodulation by Schwann cells in disease. Cancer Immunol Immunother 69, 245–253 (2020). https://doi.org/10.1007/s00262-019-02424-7

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