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:Enhancing natural killer cell anti-tumour activity through macrophage manipulation.
Enhancing natural killer cell anti-tumour activity through macrophage manipulation.
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肿瘤微环境(TME)是复杂且动态的环境,包含多种细胞、基质和可溶性因子,共同影响癌症进展、免疫逃逸和治疗耐药。在TME的免疫组分中,巨噬细胞和自然杀伤(NK)细胞是关键参与者;二者相互作用,尤其是相互通讯,对塑造抗肿瘤免疫至关重要。巨噬细胞与NK细胞的相互作用会依具体环境促进或抑制免疫应答,因此既是挑战也是治疗机遇。NK细胞是关键效应细胞,可在未预先致敏的情况下识别并清除恶性细胞;巨噬细胞则具有显著可塑性,依活化状态不同,既可促进也可抑制肿瘤免疫。本综述聚焦癌症治疗中利用巨噬细胞的当前策略,包括表型再极化、选择性清除,以及阻断或增强巨噬细胞-NK细胞相互通讯以提升NK细胞介导的肿瘤监视。最后,我们介绍单细胞RNA测序、空间转录组学和蛋白质组学等新兴技术;这些技术有助于揭示巨噬细胞与NK细胞的动态相互作用,并指导下一代免疫治疗干预。
The tumour microenvironment (TME) is a complex and dynamic environment containing diverse cellular, stromal and soluble factors, that collectively influence cancer progression, immune evasion and therapeutic resistance. Among the immune components of the TME, macrophages and natural killer (NK) cells are key players, whose interactions, particularly their crosstalk, critically shape anti-tumour immunity. The macrophage-NK cell interplay can either promote or suppress immune responses depending on the context, representing both a challenge and a therapeutic opportunity.
NK cells are key effectors capable of recognising and eliminating malignant cells without prior sensitisation, whereas macrophages exhibit remarkable plasticity, functioning as either promoters or suppressors of tumour immunity depending on their activation state. This review focuses on current strategies to harness macrophages in cancer therapy, including phenotype repolarisation, selective depletion, and disruption or enhancement of the macrophage-NK cell crosstalk to enhance NK cell-mediated tumour surveillance.
Finally, we highlight emerging technologies, such as single-cell RNA sequencing, spatial transcriptomics, and proteomics, as powerful tools to elucidate the dynamic interplay between macrophages and NK cells and inform the next generation of immunotherapeutic interventions.
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