Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype

被引：369

作者：

Gabrusiewicz, Konrad ^{[1
]}

Rodriguez, Benjamin ^{[2
,3
]}

Wei, Jun ^{[1
]}

Hashimoto, Yuuri ^{[1
]}

Healy, Luke M. ^{[4
]}

Maiti, Sourindra N. ^{[5
]}

Thomas, Ginu ^{[6
]}

Zhou, Shouhao ^{[7
]}

Wang, Qianghu ^{[8
]}

Elakkad, Ahmed ^{[6
]}

Liebelt, Brandon D. ^{[1
]}

Yaghi, Nasser K. ^{[1
]}

Ezhilarasan, Ravesanker ^{[9
]}

Huang, Neal ^{[1
]}

Weinberg, Jeffrey S. ^{[1
]}

Prabhu, Sujit S. ^{[1
]}

Rao, Ganesh ^{[1
]}

Sawaya, Raymond ^{[1
]}

Langford, Lauren A. ^{[10
]}

Bruner, Janet M. ^{[10
]}

Fuller, Gregory N. ^{[10
]}

Bar-Or, Amit ^{[4
]}

Li, Wei ^{[2
,3
]}

Colen, Rivka R. ^{[6
]}

Curran, Michael A. ^{[10
,11
]}

Bhat, Krishna P. ^{[12
]}

Antel, Jack P. ^{[4
]}

Cooper, Laurence J. ^{[5
]}

Sulman, Erik P. ^{[9
]}

Heimberger, Amy B. ^{[1
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Neurosurg, Unit 422,POB 301402, Houston, TX 77030 USA

[2] Baylor Coll Med, Div Biostat, Dan L Duncan Canc Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] McGill Univ, Neuroimmunol Unit, Dept Neurol & Neurosurg, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada

[5] Univ Texas MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX 77030 USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA

[9] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA

[10] Univ Texas MD Anderson Canc Ctr, Dept Neuropathol, Houston, TX 77030 USA

[11] Univ Texas MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA

[12] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 USA

来源：

JCI INSIGHT | 2016年 / 1卷 / 02期

关键词：

SUPPRESSOR-CELLS; HUMAN GLIOMAS; TUMOR PROGRESSION; PERIPHERAL-BLOOD; BREAST-CANCER; MYELOID CELLS; BRAIN-TUMORS; MOUSE-BRAIN; EXPRESSION; MICROGLIA;

D O I：

10.1172/jci.insight.85841

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：19

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