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

被引：457
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
收藏
页码：253 / +
页数：20
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