School of Life Science and Technology, China Pharmaceutical University, Nanjing, PR China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, PR China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108374. doi: 10.1016/j.intimp.2021.108374. Epub 2021 Nov 22.
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.
肿瘤微环境（TME）是由多种细胞类型共同构建的，包括肿瘤细胞、免疫细胞、成纤维细胞和上皮细胞等。TME 中的细胞相互作用，并与肿瘤细胞相互作用，影响肿瘤的发展和进展。作为 TME 中最丰富的免疫细胞，巨噬细胞通过大量分泌多功能细胞因子以及在表面表达一系列配体或受体与其他细胞直接相互作用来调节免疫网络。由于其强大的可塑性，它们在复杂的 TME 中发挥免疫刺激和免疫抑制作用。直接针对癌细胞的免疫系统主要效应细胞包括但不限于自然杀伤细胞（NK 细胞）、树突状细胞（DC 细胞）、巨噬细胞、多形核白细胞、肥大细胞和细胞毒性 T 淋巴细胞（CTL 细胞）。其中，NK 细胞是介导抗肿瘤和抗病毒反应的主要先天淋巴细胞亚群。NK 细胞的激活和抑制受细胞因子和激活与抑制受体之间平衡的调节。巨噬细胞和 NK 细胞之间存在着一种不可分割的调节关系。在此，我们通过可溶性介质串扰和细胞间相互作用系统地阐述了巨噬细胞和 NK 细胞之间的调节网络。我们相信，更好地了解 TME 中巨噬细胞和 NK 细胞之间的串扰将有助于开发新型以巨噬细胞或 NK 细胞为重点的治疗策略，从而在癌症治疗中具有更好的疗效。
