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:Crosstalk between macrophages and natural killer cells in the tumor microenvironment.
Crosstalk between macrophages and natural killer cells in the tumor microenvironment.
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肿瘤微环境(TME)由多种细胞共同构成,包括肿瘤细胞、免疫细胞、成纤维细胞和上皮细胞等。TME中的细胞彼此之间及其与肿瘤细胞之间相互作用,影响肿瘤发生和进展。巨噬细胞是TME中数量最多的免疫细胞,不仅可分泌多种细胞因子调控免疫网络,还可通过表面配体或受体与其他细胞直接相互作用。由于具有很强的可塑性,巨噬细胞在复杂TME中既能发挥免疫刺激作用,也可产生免疫抑制作用。直接靶向癌细胞的主要免疫效应细胞包括但不限于自然杀伤(NK)细胞、树突状细胞(DC)、巨噬细胞、多形核白细胞、肥大细胞及细胞毒性T淋巴细胞(CTL)。其中,NK细胞是介导抗肿瘤和抗病毒应答的主要先天淋巴细胞亚群。NK细胞的活化和抑制由细胞因子以及活化性与抑制性受体之间的平衡共同调控。巨噬细胞和NK细胞之间存在密切的调节关系。本文系统阐述二者通过可溶性介质通讯及细胞间相互作用构成的调控网络。
我们认为,深入理解TME中巨噬细胞与NK细胞的相互作用,将有助于开发以巨噬细胞或NK细胞为重点、疗效更好的癌症治疗策略。
The tumor microenvironment (TME) is jointly constructed by a variety of cell types, including tumor cells, immune cells, fibroblasts, and epithelial cells, among others. The cells within the TME interact with each other and with tumor cells to influence tumor development and progression. As the most abundant immune cells in the TME, macrophages regulate the immune network by not only secreting a large amount of versatile cytokines but also expressing a series of ligands or receptors on the surface to interact with other cells directly. Due to their strong plasticity, they exert both immunostimulatory and immunosuppressive effects in the complex TME.
The major effector cells of the immune system that directly target cancer cells include but are not limited to natural killer cells (NKs), dendritic cells (DCs), macrophages, polymorphonuclear leukocytes, mast cells, and cytotoxic T lymphocytes (CTLs).
Among them, NK cells are the predominant innate lymphocyte subsets that mediate antitumor and antiviral responses. The activation and inhibition of NK cells are regulated by cytokines and the balance between activating and inhibitory receptors. There is an inextricable regulatory relationship between macrophages and NK cells.
Herein, we systematically elaborate on the regulatory network between macrophages and NK cells through soluble mediator crosstalk and cell-to-cell interactions.
We believe that a better understanding of the crosstalk between macrophages and NKs in the TME will benefit the development of novel macrophage- or NK cell-focused therapeutic strategies with superior efficacies in cancer therapy.
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