TY - JOUR
T1 - Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype
AU - Gabrusiewicz, Konrad
AU - Rodriguez, Benjamin
AU - Wei, Jun
AU - Hashimoto, Yuuri
AU - Healy, Luke M.
AU - Maiti, Sourindra N.
AU - Thomas, Ginu
AU - Zhou, Shouhao
AU - Wang, Qianghu
AU - Elakkad, Ahmed
AU - Liebelt, Brandon D.
AU - Yaghi, Nasser K.
AU - Ezhilarasan, Ravesanker
AU - Huang, Neal
AU - Weinberg, Jeffrey S.
AU - Prabhu, Sujit S.
AU - Rao, Ganesh
AU - Sawaya, Raymond
AU - Langford, Lauren A.
AU - Bruner, Janet M.
AU - Fuller, Gregory N.
AU - Bar-Or, Amit
AU - Li, Wei
AU - Colen, Rivka R.
AU - Curran, Michael A.
AU - Bhat, Krishna P.
AU - Antel, Jack P.
AU - Cooper, Laurence J.
AU - Sulman, Erik P.
AU - Heimberger, Amy B.
N1 - Publisher Copyright:
© 2016 American Society for Clinical Investigation. All rights reserved.
PY - 2016/2/25
Y1 - 2016/2/25
N2 - 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.
AB - 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.
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U2 - 10.1172/jci.insight.85841
DO - 10.1172/jci.insight.85841
M3 - Article
C2 - 26973881
AN - SCOPUS:84975276172
SN - 2379-3708
VL - 1
JO - JCI Insight
JF - JCI Insight
IS - 2
M1 - e85841
ER -