RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Cowpea Mosaic Virus and Natural Killer Cell Agonism for In Situ Cancer Vaccination.
Cowpea Mosaic Virus and Natural Killer Cell Agonism for In Situ Cancer Vaccination.
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我们此前已证明植物病毒豇豆花叶病毒(CPMV)可作为有效的原位癌症疫苗,清除肿瘤并产生肿瘤特异性免疫记忆;还发现 CPMV 可募集自然杀伤(NK)细胞进入肿瘤微环境。本研究旨在确定 CPMV 联合抗 4-1BB 激动性单克隆抗体,刺激肿瘤驻留和 CPMV 募集的 NK 细胞,能否作为双重治疗策略改善 NK 细胞功能和原位癌症疫苗疗效。采用转移性结肠癌和皮内黑色素瘤小鼠模型,经瘤内给予 CPMV 加抗 4-1BB 的双重疗法,与 CPMV 或抗 4-1BB 单药相比,可产生强效抗肿瘤反应,提高原发肿瘤清除率并降低死亡率。此外,肿瘤再攻击后,肿瘤发生显著延迟或被预防,生存率提高,凸显 CPMV 联合抗 4-1BB 双重疗法可实现强效且持久的抗肿瘤疗效。
We have previously shown the plant virus Cowpea mosaic virus (CPMV) to be an efficacious in situ cancer vaccine, providing elimination of tumors and tumor-specific immune memory.
Additionally, we have shown that CPMV recruits Natural Killer (NK) cells within the tumor microenvironment.
Here we aimed to determine whether a combination of CPMV and anti-4-1BB monoclonal antibody agonist to stimulate tumor-resident and CPMV-recruited NK cells is an effective dual therapy approach to improve NK cell function and in situ cancer vaccination efficacy. Using murine models of metastatic colon carcinomatosis and intradermal melanoma, intratumorally administered CPMV + anti-4-1BB dual therapy provided a robust antitumor response, improved elimination of primary tumors, and reduced mortality compared to CPMV and anti-4-1BB monotherapies.
Additionally, on tumor rechallenge there was significant delay/prevention of tumor development and improved survival, highlighting that the CPMV + anti-4-1BB dual therapy enables potent and durable antitumor efficacy.
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