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:Leveraging the heterogeneity of the NK cell repertoire for the development of immunotherapies for acute leukemia.
Leveraging the heterogeneity of the NK cell repertoire for the development of immunotherapies for acute leukemia.
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急性白血病是一项重大的治疗挑战,需要开发创新性方法以改善患者的临床结局。免疫治疗已成为急性白血病治疗的支柱。异基因造血干细胞移植(allo-HSCT)是一种成熟且有效的操作。随着时间推移,许多治疗策略已作为实现持久缓解的有前景策略出现,并改变了白血病的治疗。在抗击白血病的有效免疫细胞中,自然杀伤(NK)细胞是固有细胞毒性细胞,不需要抗原特异性即可发挥其细胞毒性功能。NK细胞作为白血病患者治疗的潜力正成为一种有前景的方法。由于众多抑制性和激活性受体之间的精细平衡,它们能够以天然方式区分健康细胞和白血病细胞。近年来,已发现NK细胞远比预期复杂。事实上,NK细胞库表现出显著高度的表型多样性,这与免疫遗传学 KIR 和 HLA I类标志物的广泛多态性密切相关。已证明并非所有NK细胞具有相同的功能谱,并且它们对这些KIR-HLA分子相互作用介导的功能教育作出反应。本综述提供对NK细胞多样性认识的见解,目标是利用NK细胞异质性来开发用于急性白血病的NK细胞免疫治疗。
Acute leukemia represents a significant therapeutic challenge, necessitating the development of innovative approaches to improve the clinical outcomes of patients. Immunotherapies have become a mainstay in the treatment of acute leukemia. Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a well-established and efficacious procedure. Over time, a number of therapeutic approaches have emerged as promising strategies for achieving durable remission and have transformed the treatment of leukemia. Among the efficient immune cells engaged against leukemia, natural killer (NK) cells are innate cytotoxic cells that do not require antigenic specificity to exert their cytotoxic function. The potential of NK cells as a treatment for leukemic patients is emerging as a promising approach.
They are capable of distinguishing between healthy and leukemic cells in a natural manner because of the sophisticated equilibrium between their numerous inhibitory and activating receptors. In recent years, NK cells have been found to be far more complex than expected. Indeed, the NK repertoire exhibits a remarkably high degree of phenotypic diversity, which is closely linked to the extensive polymorphism of immunogenetic KIR and HLA class I markers.
It has been demonstrated that not all NK cells possess the same functional profile and that they respond to functional education mediated by these KIR-HLA molecular interactions. This review offers insights into the knowledge of NK cell diversity, with the goal of leveraging NK cell heterogeneity for the development of NK cell-based immunotherapies for acute leukemia.
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