ICOS:肿瘤免疫新靶点
  • 用Newcastle疾病病毒(NDV)进行肿瘤内治疗,除了激活天然免疫、上调T细胞共刺激因子受体的表达,还伴随诱导性共刺激因子(ICOS);
  • 采用基因工程表达NDV的ICOS配体(NDV-ICOSL);
  • 有双侧肿瘤模型中,肿瘤内给予NDV-ICOSL导致病毒注射侧和远处肿瘤内活化T细胞浸润增加,当与全身性CTLA-4阻断剂联合应用时,对双侧肿瘤产生明显的疗效;
  • 用表达合理选择的配体的溶瘤病毒进行肿瘤内免疫调控,可成为驱动免疫检查点抑制剂全身疗效的有效方法。
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Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity

重组溶瘤病毒在肿瘤内调控诱导性共刺激因子ICOS促进全身性抗肿瘤免疫

10.1038/ncomms14340

2017-02-13, Article

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Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive systemic efficacy of immune checkpoint blockade.

First Authors:
Dmitriy Zamarin

Correspondence Authors:
Dmitriy Zamarin

All Authors:
Dmitriy Zamarin,Rikke B Holmgaard,Jacob Ricca,Tamar Plitt,Peter Palese,Padmanee Sharma,Taha Merghoub,Jedd D Wolchok,James P Allison

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