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Schwann cells shape the neuro-immune environs and control cancer progression

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Abstract

At present, significant experimental and clinical data confirm the active involvement of the peripheral nervous system (PNS) in different phases of cancer development and progression. Most of the research effort focuses on the impact of distinct neuronal types, e.g., adrenergic, cholinergic, dopaminergic, etc. in carcinogenesis, generally ignoring neuroglia. The very fact that these cells far outnumber the other cellular types may also play an important role worthy of study in this context. The most prevalent neuroglia within the PNS consists of Schwann cells (SCs). These cells play a substantial role in maintaining homeostasis within the nervous system. They possess distinct immunomodulatory, inflammatory and regenerative capacities—also, one should consider their broad distribution throughout the body; this makes them a perfect target for malignant cells during the initial stages of cancer development and the very formation of the tumor microenvironment itself. We show that SCs in the tumor milieu attract different subsets of immune regulators and augment their ability to suppress effector T cells. SCs may also up-regulate invasiveness of tumor cells and support metastatic disease. We outline the interactive potential of SCs juxtaposed with cancerous cells, referring to data from various external sources alongside data of our own.

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Abbreviations

CNS:

Central nervous system

DFTD:

Devil facial tumor disease

DRG:

Dorsal root ganglion

EMT:

Epithelial–mesenchymal transition

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

HMGB1:

High-mobility group box 1

MAG:

Myelin-associated glycoprotein

MDSC:

Myeloid-derived suppressor cell(s)

MET:

Mesenchymal–epithelial transition

NB:

Neuroblastoma

Nrg:

Neuregulin

PGP 9.5:

Protein gene product 9.5

PNI:

Perineural invasion

PNS:

Peripheral nervous system

SC:

Schwann cell(s)

SDF-1α:

Stromal cell-derived factor 1 (CXCL12)

SPARC:

Secreted protein acidic and rich in cysteine

TµE:

Tumor microenvironment

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Funding

This work was supported by London Foundation Grant (to M. R. Shurin) and University of Pittsburgh Cancer Institute (UPCI) Melanoma and SPORE in Skin Cancer Career Enhancement Program Award NIH P50CA121973 (to Y. L. Bunimovich).

Author information

Authors and Affiliations

  1. Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    German V. Martyn

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

    Galina V. Shurin & Michael R. Shurin

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

    Michael R. Shurin

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

    Yuri L. Bunimovich

  5. Centre for Strategic Planning and Management of Biomedical Health Risks, Ministry of Health, Moscow, Russia

    Anton A. Keskinov

  6. Clinical Immunopathology, University of Pittsburgh Medical Center, Clinical Lab Bldg, Room 4024, 3477 Euler Way, Pittsburgh, PA, 15213, USA

    Michael R. Shurin

Authors
  1. German V. Martyn
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  2. Galina V. Shurin
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  3. Anton A. Keskinov
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  4. Yuri L. Bunimovich
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  5. Michael R. Shurin
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Contributions

Conceptualization, MRS, AAK and YLB; Methodology, GVS, and MRS; Investigation, GVS and YLB; Writing —Original Draft, GVM and MRS; Writing—Review and Editing, GVM and MRS; Funding Acquisition, MRS and YLB; Resources, MRS and AAK; Supervision, GVS and MRS.

Corresponding author

Correspondence to Michael R. Shurin.

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The author reports no conflicts of interest in this work.

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Martyn, G.V., Shurin, G.V., Keskinov, A.A. et al. Schwann cells shape the neuro-immune environs and control cancer progression. Cancer Immunol Immunother 68, 1819–1829 (2019). https://doi.org/10.1007/s00262-018-02296-3

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  • DOI: https://doi.org/10.1007/s00262-018-02296-3

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