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 citas
Etiquetas de revisión
Solo mecanismosDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio in vitro o de mecanismos (clasificado por nuestro filtro de IA)
- Estudiado en
- Células o muestras de laboratorio
- Resultado principal
- Solo mecanismos
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Brain Tumor Funders' Collaborative
- Gobierno
- National Institutes of Health
- Gobierno
- National Institute of Neurological Disorders and Stroke
- Gobierno
- NINDS NIH HHS
- Organización sin fines de lucro
- Brains Together for a Cure
- Subvenciones
- National Institute of Neurological Disorders and Stroke (T32 NS007494); National Institutes of Health (T32NS07494)
Según 5 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2017-06-30 · PLoS One · vol. 12 · número 6 · pág. e0179012
- Editorial
- Public Library of Science
- Citado
- 70 citas · más que el 92% de estudios similares · 3.0× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 80 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Macrophage Migration Inhibitory Factor · Immune cells in cancer · Reproductive System and Pregnancy
- Palabras clave
- 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 autores
- Ravi Kumar🇺🇸Mayo Clinic; Neurological Surgery
- Tristan de Mooij🇺🇸Mayo Clinic; Neurological Surgery
- Timothy E. Peterson🇺🇸Mayo Clinic; Neurological Surgery
- Tatiana Kaptzan🇺🇸Mayo Clinic; Neurological Surgery
- Aaron J. Johnson🇺🇸Mayo Clinic
- David J. Daniels🇺🇸Mayo Clinic; Neurological Surgery
- Ian F. Parney🇺🇸 · autor de correspondenciaMayo Clinic; Neurological Surgery
Resumen
El texto original del estudio, en el idioma en que se publicó.
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.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
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