Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heter...

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Vydáno v:JCI insight Ročník 1; číslo 2
Hlavní autoři: Gabrusiewicz, Konrad, Rodriguez, Benjamin, Wei, Jun, Hashimoto, Yuuri, Healy, Luke M., Maiti, Sourindra N., Thomas, Ginu, Zhou, Shouhao, Wang, Qianghu, Elakkad, Ahmed, Liebelt, Brandon D., Yaghi, Nasser K., Ezhilarasan, Ravesanker, Huang, Neal, Weinberg, Jeffrey S., Prabhu, Sujit S., Rao, Ganesh, Sawaya, Raymond, Langford, Lauren A., Bruner, Janet M., Fuller, Gregory N., Bar-Or, Amit, Li, Wei, Colen, Rivka R., Curran, Michael A., Bhat, Krishna P., Antel, Jack P., Cooper, Laurence J., Sulman, Erik P., Heimberger, Amy B.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Society for Clinical Investigation 25.02.2016
ISSN:2379-3708, 2379-3708
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Abstract Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.
AbstractList Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.
Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.
Author Ezhilarasan, Ravesanker
Curran, Michael A.
Weinberg, Jeffrey S.
Thomas, Ginu
Bruner, Janet M.
Li, Wei
Cooper, Laurence J.
Yaghi, Nasser K.
Heimberger, Amy B.
Antel, Jack P.
Wei, Jun
Gabrusiewicz, Konrad
Sulman, Erik P.
Rao, Ganesh
Langford, Lauren A.
Fuller, Gregory N.
Wang, Qianghu
Maiti, Sourindra N.
Prabhu, Sujit S.
Bar-Or, Amit
Colen, Rivka R.
Elakkad, Ahmed
Liebelt, Brandon D.
Hashimoto, Yuuri
Huang, Neal
Sawaya, Raymond
Healy, Luke M.
Rodriguez, Benjamin
Bhat, Krishna P.
Zhou, Shouhao
AuthorAffiliation 1 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
3 Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
9 Department of Neuropathology
10 Department of Immunology, and
7 Department of Bioinformatics and Computational Biology
8 Department of Radiation Oncology
6 Department of Biostatistics
11 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
2 Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
5 Department of Diagnostic Radiology
4 Division of Pediatrics
AuthorAffiliation_xml – name: 5 Department of Diagnostic Radiology
– name: 8 Department of Radiation Oncology
– name: 10 Department of Immunology, and
– name: 2 Division of Biostatistics, Dan L. Duncan Cancer Center and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA
– name: 3 Neuroimmunology Unit, Department of Neurology and Neurosurgery, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada
– name: 4 Division of Pediatrics
– name: 6 Department of Biostatistics
– name: 7 Department of Bioinformatics and Computational Biology
– name: 9 Department of Neuropathology
– name: 1 Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
– name: 11 Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/26973881$$D View this record in MEDLINE/PubMed
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Snippet Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the...
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