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:NK cell activity in the tumor microenvironment.
NK cell activity in the tumor microenvironment.
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免疫抑制性肿瘤微环境(TME)的形成会损害自然杀伤(NK)细胞在肿瘤组织内的浸润和持久性,并显著降低NK细胞介导的细胞毒性。这构成了NK细胞疗法在实体瘤中疗效的重大障碍。当前的策略旨在通过增强NK细胞的识别和细胞毒性来克服免疫逃逸,同时促进其持久性、浸润能力以及对TME的抵抗力。本综述聚焦于TME的生物物理特征以及影响NK细胞活性的细胞外基质(ECM)特定组分,目标是确定调节TME并为适应性免疫细胞功能创造支持性微环境的治疗策略。整合肿瘤学、细胞生物学、物理学、工程学、材料科学和纳米技术的跨学科合作进展,对于推进靶向ECM硬度和机械转导信号通路的治疗策略至关重要。
The formation of an immunosuppressive tumor microenvironment (TME) impairs natural killer (NK) cell infiltration and persistence within tumor tissue and significantly diminishes NK-mediated cytotoxicity. This presents a substantial barrier to the efficacy of NK cell therapy in solid tumors. Current strategies aim to overcome immune evasion by enhancing NK cell recognition and cytotoxicity, while promoting their persistence, infiltration, and resistance to the TME.
This review focusses on the biophysical characteristics of TME and specific components of the extracellular matrix (ECM) that affect NK cell activity, with the goal of identifying therapeutic approaches to modulate the TME and create a supportive niche for adaptive immune cell function. Advancements in interdisciplinary collaborations integrating oncology, cell biology, physics, engineering, materials science, and nanotechnology are crucial in advancing therapeutic strategies targeting ECM rigidity and mechanotransduction signaling pathways.
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