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 the power of memory-like NK cells to fight cancer.
Harnessing the power of memory-like NK cells to fight cancer.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
自然杀伤(NK)细胞具有有效消灭癌细胞的先天能力。其在免疫监视中的关键作用已被广泛认可并用于治疗干预。尽管NK细胞具有快速起效的特性,但NK过继细胞转移在某些患者中缺乏良好的应答。患者的NK细胞往往表现出预防癌症进展的表型减弱,导致预后不良。肿瘤微环境在导致患者NK细胞功能衰退中起着重要作用。肿瘤微环境释放的抑制因子阻碍了NK细胞抗肿瘤的正常功能。为克服这一挑战,正在研究细胞因子刺激和基因操作等治疗策略以提高NK细胞的杀肿瘤能力。其中一种有前景的方法是通过ex vivo细胞因子激活和增殖生成更具效能的NK细胞。细胞因子诱导的ML-NK表现出表型改变,如活化受体表达增强,有助于提升其抗肿瘤应答。既往临床前研究显示,与正常NK细胞相比,ML-NK细胞对恶性细胞具有增强的细胞毒性和IFNγ产生。临床研究中也显示了类似效果,其中MK-NK在治疗血液系统恶性肿瘤方面表现出令人鼓舞的结果。
然而,仍缺乏使用ML-NK治疗不同类型肿瘤和癌症的深入研究。凭借令人信服的初步应答,这种基于细胞的方法可用于补充其他治疗方式以取得更好的临床结局。
Natural killer (NK) cells possess the innate ability to eliminate cancerous cells effectively. Their crucial role in immunosurveillance has been widely recognized and exploited for therapeutic intervention. Despite the fast-acting nature of NK cells, NK adoptive cell transfer lacks favorable response in some patients. Patient NK cells often display diminished phenotype in preventing cancer progression resulting in poor prognosis. Tumor microenvironment plays a significant role in causing the downfall of NK cells in patients. The release of inhibitory factors by tumor microenvironment hinders normal function of NK cells against tumor.
To overcome this challenge, therapeutic strategies such as cytokine stimulation and genetic manipulation are being investigated to improve NK tumor-killing capacity. One of the promising approaches includes generation of more competent NK cells via ex vivo cytokines activation and proliferation.
Cytokine-induced ML-NK demonstrated phenotypic alterations such as enhanced expression of activating receptors which help elevate their antitumor response. Previous preclinical studies showed enhanced cytotoxicity and IFNγ production in ML-NK cells compared to normal NK cells against malignant cells. Similar effects are shown in clinical studies in which MK-NK demonstrated encouraging results in treating hematological cancer.
However, there is still a lack of in-depth studies using ML-NK in treating different types of tumors and cancers. With convincing preliminary response, this cell-based approach could be used to complement other therapeutic modalities to achieve better clinical outcomes.
MEMBER ACCOUNT
登录成功会直接打开下一页。