Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

被引：258

作者：

Zhang, Michael ^{[1
]}

Hutter, Gregor ^{[1
,2
,3
]}

Kahn, Suzana A. ^{[1
,2
,3
]}

Azad, Tej D. ^{[1
]}

Gholamin, Sharareh ^{[1
,2
,3
]}

Xu, Chelsea Y. ^{[1
]}

Liu, Jie ^{[2
]}

Achrol, Achal S. ^{[1
]}

Richard, Chase ^{[1
]}

Sommerkamp, Pia ^{[1
,2
,3
]}

Schoen, Matthew Kenneth ^{[1
]}

McCracken, Melissa N. ^{[2
]}

Majeti, Ravi ^{[2
,3
]}

Weissman, Irving ^{[2
,3
]}

Mitra, Siddhartha S. ^{[1
,2
,3
]}

Cheshier, Samuel H. ^{[1
,2
,3
]}

机构：

[1] Stanford Univ, Div Pediat Neurosurg, Dept Neurosurg, Lucile Packard Childrens Hosp,Sch Med, Stanford, CA 94305 USA

[2] Stanford Univ, Inst Stem Cell Biol & Regenerat Med, Sch Med, Stanford, CA 94305 USA

[3] Stanford Univ, Ludwig Ctr Canc Stem Cell Res & Med Stanford, Sch Med, Stanford, CA 94305 USA

来源：

PLOS ONE | 2016年 / 11卷 / 04期

基金：

瑞士国家科学基金会;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; REGULATORY PROTEIN-ALPHA; HEMATOPOIETIC STEM-CELLS; SIRP-ALPHA; APOPTOTIC CELLS; CANCER-CELLS; GM-CSF; CD47; SURVIVAL; PROGRESSION;

D O I：

10.1371/journal.pone.0153550

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow -derived mouse macrophages and peripheral blood derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor -cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid 112rgtmlwil ISzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

引用

页数：21

共 59 条

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