肿瘤微环境
癌症研究
CD8型
免疫系统
结直肠癌
医学
血管生成
内科学
细胞毒性T细胞
联合疗法
血管内皮生长因子
免疫学
药理学
癌症
化学
体外
血管内皮生长因子受体
生物化学
作者
Yuanyuan Wang,Bin Wei,Jianhua Gao,Xiaomin Cai,Lingyan Xu,Haiqing Zhong,Binglin Wang,Yang-Kook Sun,Wenjie Guo,Qiang Xu,Yanhong Gu
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2020-10-07
卷期号:205 (10): 2905-2915
被引量:25
标识
DOI:10.4049/jimmunol.2000463
摘要
Identification of effective therapies for colorectal cancer (CRC) remains an urgent medical need, especially for the microsatellite-stable (MSS) phenotype. In the current study, a combination of fruquintinib plus anti-PD-1 for MSS CRC therapy was investigated. First, a case of advanced MSS CRC was reported. After failure of multiline therapy, the patient finally achieved rapid response after receiving fruquintinib plus anti-PD-1 treatment. Then the effect of fruquintinib plus anti-PD-1 was verified using a murine syngeneic model of CT26 cells (MSS). The results showed that cotreatment significantly inhibited tumor growth and promote survival time for tumor-bearing mice compared with the single drug alone. In addition, fruquintinib/anti-PD-1 cotreatment decreased angiogenesis, enhanced normalization of the vascular structure, and alleviated tumor hypoxia. Moreover, the combination therapy reprogrammed the immune microenvironment by enhancing chemotactic factor release, increasing CD8+ T cell infiltration and activation, decreasing ration of regulatory T cells, and promoting M1/M2 ratio of macrophage. Finally, the enhanced antitumor effect of fruquintinib/anti-PD-1 cotreatment was significantly reversed in CD8 knockout mice compared with that in the wild-type mice. Our study indicated that combination of fruquintinib and anti-PD-1 could synergistically suppress CRC progression and altered the tumor microenvironment in favor of antitumor immune responses.
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