Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade.
Macrophage Polarization Contributes to Glioblastoma Eradication by Combination Immunovirotherapy and Immune Checkpoint Blockade.
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巨噬细胞极化有助于通过免疫疗法和免疫检查点阻断来消除胶质母细胞瘤。
DOI：
10.1016/j.ccell.2017.07.006
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发表时间：
2017-08-14
期刊：
影响因子：
50.3
通讯作者：
Rabkin SD
中科院分区：
文献类型：
--
作者：
Saha D;Martuza RL;Rabkin SD
胶质母细胞瘤是一种免疫抑制的致命脑癌，含有胶质母细胞瘤干细胞(GSCs)。溶瘤单纯疱疹病毒(OHSV)在癌细胞中选择性复制，同时诱导抗肿瘤免疫。表达小鼠IL-12的OHSV G47Δ(G47Δ-mIL12)、免疫检查点抗体(CTLA-4、PD-1、PD-L1)或双重组合可适度延长小鼠胶质瘤模型的存活。然而，在两种胶质瘤模型中，抗CTLA-4、抗PD-1和G47Δ-mIL12的三重组合治愈了大部分小鼠。这种治疗与巨噬细胞内流和M1样极化以及T效应与T调节细胞比率的增加有关。免疫细胞耗竭研究表明，协同治疗活性需要CD4+和CD8+T细胞以及巨噬细胞。这种组合应该可以翻译到临床和其他免疫抑制癌症。Saha等人。结果表明，表达IL-12的溶瘤病毒与两种免疫检查点抑制剂--抗CTLA-4和抗PD1抗体--相结合，可以在两种小鼠模型中根除胶质瘤。联合治疗的疗效取决于CD4+和CD8+T细胞以及巨噬细胞。
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 G47Δ expressing murine IL-12 (G47Δ-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 G47Δ-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. Saha et al. show that the combination of an oncolytic virus expressing IL-12 with two immune checkpoint inhibitors, anti-CTLA-4 and anti-PD1 antibodies, can eradicate glioma in two mouse models. The therapeutic efficacy of the combination treatment depends on CD4+ and CD8+ T cells as well as macrophages.
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影响因子：
6.4
作者：
Le, Dung T.;Ladle, Brian H.;Lee, Timothy;Weiss, Vivian;Yao, Xiaosai;Leubner, Ashley;Armstrong, Todd D.;Jaffee, Elizabeth M.
通讯作者：
Jaffee, Elizabeth M.
DOI：
10.1097/cji.0b013e3182562d59
发表时间：
2012-06
期刊：
Journal of immunotherapy (Hagerstown, Md. : 1997)
影响因子：
--
作者：
Agarwalla P;Barnard Z;Fecci P;Dranoff G;Curry WT Jr
通讯作者：
Curry WT Jr
DOI：
10.1097/nen.0000000000000210
发表时间：
2015-07
影响因子：
3.2
作者：
Nigim F;Cavanaugh J;Patel AP;Curry WT Jr;Esaki S;Kasper EM;Chi AS;Louis DN;Martuza RL;Rabkin SD;Wakimoto H
通讯作者：
Wakimoto H
DOI：
10.1084/jem.20130678
发表时间：
2013-12-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Vom Berg J;Vrohlings M;Haller S;Haimovici A;Kulig P;Sledzinska A;Weller M;Becher B
通讯作者：
Becher B
影响因子：
7.3
作者：
Haabeth OA;Tveita AA;Fauskanger M;Schjesvold F;Lorvik KB;Hofgaard PO;Omholt H;Munthe LA;Dembic Z;Corthay A;Bogen B
通讯作者：
Bogen B