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:Harnessing Natural Killer Cell-Mediated Innate Immune Responses for Cancer Treatment: Advances and Challenges.
Harnessing Natural Killer Cell-Mediated Innate Immune Responses for Cancer Treatment: Advances and Challenges.
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自然杀伤(NK)细胞是机体抵御癌症和感染的先天防御系统的守门人。我们和其他人越来越多的文献发现,NK细胞促进抗癌免疫监视,而NK细胞发育缺陷与癌症临床预后不良相关。在临床前研究中,发现NK细胞可驱动肿瘤消退并延缓肿瘤复发。由于NK细胞对机体的潜在损伤较小,且比基于T细胞的疗法更易开发,目前正努力提高NK细胞的细胞毒性和体内持久性,以用作过继性、现货型免疫疗法。在这篇综述中,我们讨论肿瘤内在和外在因素如何在癌症微环境中抑制NK细胞。我们还概述了恢复癌症中NK监视的当前策略以及基于NK细胞疗法的临床使用所面临的挑战。
Natural killer (NK) cells are a gatekeeper of the body's innate defense system against cancers and infections. A growing body of literature from us and others finds that NK cells promote anti-cancer immune surveillance, and that defects in NK cell development are associated with poor clinical prognosis of cancers. In preclinical studies, NK cells were found to drive tumor regression and delay tumor relapse.
Because NK cells are potentially less damaging to the body and are easier to develop than T cell-based therapies, efforts are being made to improve NK cell cytotoxicity and in vivo persistence for use as an adoptive, off-the-shelf immunotherapy. In this review, we discuss how tumor-intrinsic and -extrinsic factors suppress NK cells in the cancer microenvironment.
We also outline current strategies that restore NK surveillance in cancer and challenges facing the clinical use of NK cell-based therapies.
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