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:Natural killer cell-based immunotherapy for cancer.
Natural killer cell-based immunotherapy for cancer.
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自然杀伤(NK)细胞凭借先天性选择识别并清除癌细胞的能力,正成为癌症免疫治疗的有前景工具。过去30年来,利用NK细胞的策略包括细胞因子、小分子、抗体以及自体或异体NK细胞过继转移,细胞可未经改造或经基因工程改造。尽管临床试验显示其安全性良好,但体内持续时间有限、细胞耗竭及抑制性肿瘤微环境等挑战仍妨碍其疗效和持久性。本综述将NK细胞疗法分为三大类:(1)细胞疗法,包括未改造及嵌合抗原受体工程化NK细胞;(2)细胞因子策略,如白细胞介素2和白细胞介素15衍生物;(3)抗体疗法,包括免疫检查点抑制剂和NK细胞衔接器。本文概述这些进展,讨论现有限制,并提出优化NK细胞疗法、改善癌症治疗结局的策略。
Natural killer (NK) cells are emerging as a promising tool for cancer immunotherapy due to their innate ability to selectively recognize and eliminate cancer cells. Over the past 3 decades, strategies to harness NK cells have included cytokines, small molecules, antibodies, and the adoptive transfer of autologous or allogeneic NK cells, both unmodified and genetically engineered.
Despite favorable safety profiles in clinical trials, challenges such as limited in vivo persistence, exhaustion, and the suppressive tumor microenvironment continue to hinder their efficacy and durability. This review categorizes NK cell-based therapies into 3 major approaches: (i) cellular therapies, including unmodified and chimeric antigen receptor-engineered NK cells; (ii) cytokine-based strategies such as interleukin-2 and interleukin-15 derivatives; and (iii) antibody-based therapies, including immune checkpoint inhibitors and NK cell engagers.
We highlight these advancements, discuss current limitations, and propose strategies to optimize NK cell-based therapies for improved cancer treatment outcomes.
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