期刊
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
卷 172, 期 3, 页码 500-506出版社
WILEY
DOI: 10.1111/cei.12069
关键词
anti-angiogenesis; anti-tumour immunity; immune checkpoint; PD-1; VEGFR2
类别
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19591491, 21591648]
- Pancreas Research Foundation of Japan
- Foundation for Promotion of Cancer Research in Japan
- Daiwa Securities Health Foundation
- Japanese Society of Gastroenterology
- Nakayama Cancer Research Institute
- Grants-in-Aid for Scientific Research [21591648, 24591887, 19591491, 22240089] Funding Source: KAKEN
Recent basic and clinical studies have shown that the programmed death ligand (PD-L)/PD-1 pathway has a significant role in tumour immunity, and its blockade has a therapeutic potential against several human cancers. We hypothesized that anti-angiogeneic treatment might augment the efficacy of PD-1 blockade. To this end, we evaluated combining the blockade of PD-1 and vascular endothelial growth factor receptor 2 (VEGFR2) in a murine cancer model using Colon-26 adenocarcinoma. Interestingly, simultaneous treatment with anti-PD-1 and anti-VEGFR2 monoclonal antibodies (mAbs) inhibited tumour growth synergistically in vivo without overt toxicity. Blocking VEGFR2 inhibited tumour neovascularization significantly, as demonstrated by the reduced number of microvessels, while PD-1 blockade had no impact on tumour angiogenesis. PD-1 blockade might promote T cell infiltration into tumours and significantly enhanced local immune activation, as shown by the up-regulation of several proinflammatory cytokine expressions. Importantly, VEGFR2 blockade did not interfere with T cell infiltration and immunological activation induced by PD-1 blockade. In conclusion, simultaneous blockade of PD-1 and VEGFR2 induced a synergistic in-vivo anti-tumour effect, possibly through different mechanisms that might not be mutually exclusive. This unique therapeutic strategy may hold significant promise for future clinical application.
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