Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade

被引：475

作者：

Saha, Dipongkor ^{[1
,2
,3
]}

Martuza, Robert L. ^{[1
,2
,3
]}

Rabkin, Samuel D. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Dept Neurosurg, Mol Neurosurg Lab, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Boston, MA 02114 USA

[3] Harvard Med Sch, Dept Neurosurg, Boston, MA 02115 USA

来源：

CANCER CELL | 2017年 / 32卷 / 02期

关键词：

CANCER STEM-CELLS; TUMOR-ASSOCIATED MACROPHAGES; REGULATORY T; TALIMOGENE LAHERPAREPVEC; GLIOMA; VIRUS; IPILIMUMAB; IMMUNOTHERAPY; THERAPY; MODEL;

D O I：

10.1016/j.ccell.2017.07.006

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47 Delta expressing murine IL-12 (G47 Delta-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47 Delta-mIL12 cured most mice in two glioma models. This treatment was associated with macrophage influx and M1-like polarization, along with increased T effector to T regulatory cell ratios. Immune cell depletion studies demonstrated that CD4(+) and CD8(+) T cells as well as macrophages are required for synergistic curative activity. This combination should be translatable to the clinic and other immunosuppressive cancers.

引用

页码：253 / +

页数：20

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