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:A promising antitumor method: Targeting CSC with immune cells modified with CAR.
A promising antitumor method: Targeting CSC with immune cells modified with CAR.
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肿瘤严重威胁人类健康。作为肿瘤细胞中的一个亚群,癌症干细胞(CSC)具有更强的增殖和多向分化能力,可参与肿瘤发生、发展、转移和复发。因此,抑制CSC是肿瘤治疗的关键环节。研究人员已提出多种抑制或减少CSC的方法,包括靶向CSC特异性表面分子的单克隆抗体、信号通路抑制剂、能量代谢酶抑制剂以及诱导分化治疗等。此外,采用嵌合抗原受体(CAR)工程化免疫细胞的免疫治疗也已显示出良好效果,但这一领域尚缺乏全面综述。本文总结近期用于抑制CSC的靶点,以及用于CSC治疗的不同CAR工程化免疫效应细胞,包括T细胞、自然杀伤(NK)细胞和巨噬细胞。最后,文章列出CAR免疫治疗靶向CSC的主要挑战和可选策略。联合靶向两种肿瘤抗原(一种CSC抗原和一种成熟肿瘤细胞共有抗原)的设计可能更合理、更实用;本文同时强调CAR-NK在肿瘤治疗中的潜力。
Tumors pose a great threat to human health; as a subgroup of tumor cells, cancer stem cells (CSCs) contribute to the genesis, development, metastasis, and recurrence of tumors because of their enhanced proliferation and multidirectional differentiation.
Thus, a critical step in tumor treatment is to inhibit CSCs. Researchers have proposed many methods to inhibit or reduce CSCs, including monoclonal antibodies targeting specific surface molecules of CSCs, signal pathway inhibitors, and energy metabolic enzyme inhibitors and inducing differentiation therapy.
Additionally, immunotherapy with immune cells engineered with a chimeric antigen receptor (CAR) showed favorable results.
However, there are few comprehensive reviews in this area. In this review, we summarize the recent CSC targets used for CSC inhibition and the different immune effector cells (T cells, natural killer (NK) cells, and macrophages) which are engineered with CAR used for CSC therapy.
Finally, we list the main challenges and options in targeting CSC with CAR-based immunotherapy. The design targeting two tumor antigens (one CSC antigen and one mature common tumor antigen) should be more reasonable and practical; meanwhile, we highlight the potential of CAR-NK in tumor treatment.
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