Modulating glioma-mediated myeloid-derived suppressor cell development with sulforaphane
Kumar R, de Mooij T, Peterson TE, Kaptzan T, Johnson AJ, Daniels DJ, Parney IF
PloS one · 62 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Nonprofit
- Brain Tumor Funders' Collaborative
- Government
- National Institutes of Health
- Government
- National Institute of Neurological Disorders and Stroke
- Government
- NINDS NIH HHS
- Nonprofit
- Brains Together for a Cure
- Grants
- National Institute of Neurological Disorders and Stroke (T32 NS007494); National Institutes of Health (T32NS07494)
Based on 5 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2017-06-30 · PLoS One · vol. 12 · issue 6 · p. e0179012
- Publisher
- Public Library of Science
- Cited
- 70 citations · more than 92% of similar papers · 3.0× the field average
- Impact
- Top 10% most cited in its field
- References
- 80 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Macrophage Migration Inhibitory Factor · Immune cells in cancer · Reproductive System and Pregnancy
- Keywords
- Myeloid-derived Suppressor Cell, Sulforaphane, Cancer research, Immunology, Glioma, Dendritic cell, Biology, Monocyte, Cytokine, Immune system, Chemistry, Suppressor, Cancer
- MeSH
- cell line, tumor, humans, glioblastoma, brain neoplasms, isothiocyanates, sulfoxides, fucosyltransferases, culture media, conditioned, cell hypoxia, myeloid-derived suppressor cells, lewis x antigen, cd11b antigen
7 authors
From US
- Ravi KumarMayo Clinic; Neurological Surgery
- Tristan de MooijMayo Clinic; Neurological Surgery
- Timothy E. PetersonMayo Clinic; Neurological Surgery
- Tatiana KaptzanMayo Clinic; Neurological Surgery
- Aaron J. JohnsonMayo Clinic
- David J. DanielsMayo Clinic; Neurological Surgery
Abstract
Glioblastoma is the most common primary tumor of the brain and has few long-term survivors. The local and systemic immunosuppressive environment created by glioblastoma allows it to evade immunosurveillance. Myeloid-derived suppressor cells (MDSCs) are a critical component of this immunosuppression. Understanding mechanisms of MDSC formation and function are key to developing effective immunotherapies. In this study, we developed a novel model to reliably generate human MDSCs from healthy-donor CD14+ monocytes by culture in human glioma-conditioned media. Monocytic MDSC frequency was assessed by flow cytometry and confocal microscopy. The resulting MDSCs robustly inhibited T cell proliferation. A cytokine array identified multiple components of the GCM potentially contributing to MDSC generation, including Monocyte Chemoattractive Protein-1, interleukin-6, interleukin-8, and Macrophage Migration Inhibitory Factor (MIF). Of these, Macrophage Migration Inhibitory Factor is a particularly attractive therapeutic target as sulforaphane, a naturally occurring MIF inhibitor derived from broccoli sprouts, has excellent oral bioavailability. Sulforaphane inhibits the transformation of normal monocytes to MDSCs by glioma-conditioned media in vitro at pharmacologically relevant concentrations that are non-toxic to normal leukocytes. This is associated with a corresponding increase in mature dendritic cells. Interestingly, sulforaphane treatment had similar pro-inflammatory effects on normal monocytes in fresh media but specifically increased immature dendritic cells. Thus, we have used a simple in vitro model system to identify a novel contributor to glioblastoma immunosuppression for which a natural inhibitor exists that increases mature dendritic cell development at the expense of myeloid-derived suppressor cells when normal monocytes are exposed to glioma conditioned media.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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