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:Adjusting the scope of natural killer cells in cancer therapy.
Adjusting the scope of natural killer cells in cancer therapy.
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自然杀伤(NK)细胞演化出识别组织异常的能力;组织异常可由病原体感染、基因组损伤或细胞转化引起。NK细胞会迅速应答,产生强效促炎和细胞溶解介质。急性促炎应答能够在数日内高效协调针对病原体的灭菌性免疫,但细胞转化常可逃避NK细胞的先天识别机制。当细胞转化发展为恶性肿瘤时,肿瘤细胞和/或肿瘤微环境还可演化出其他机制以规避NK细胞应答;目前癌症已成为全球主要疾病负担。本文综述恶性肿瘤与自然杀伤(NK)细胞相互关系的最新认识,从近期靶向NK细胞治疗癌症的临床实践中汲取经验,并概述旨在改善癌症先天免疫应答的一些新兴治疗理念。
Natural killer (NK) cells have evolved to detect abnormalities in tissues arising from infection with pathogens, genomic damage, or transformation and respond rapidly to the production of potent proinflammatory and cytolytic mediators.
While this acute proinflammatory response is highly efficient at orchestrating sterilizing immunity to pathogens in a matter of days, cellular transformation often avoids the innate detection mechanisms of NK cells. When cellular transformation results in malignancy, tumor cells and/or the tumor microenvironment can evolve additional mechanisms to circumvent NK cell responses, and cancer is now a dominant disease burden worldwide.
Here, we review recent advances in our understanding of the combined relationship between malignancies and natural killer (NK) cells, learn from recent clinical efforts in therapeutically targeting natural killer (NK) cells in cancer and outline some emerging therapeutic concepts that aim to improve the innate immune response against cancer.
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