Fig. 3.

Crosstalk between NK cells and the TME. In the TME, complex crosstalk exists between NK cells and key cellular components in TME, and this interaction affects their respective cellular functions (left panel). In the intricate TME, exposure to enhancement signals promotes NK cell antitumor responses, and conversely, exposure to inhibitory signals puts NK cells in an immunosuppressive state. NK cells are in a dynamic microenvironment, and the functional transition that occurs when NK cells crosstalk with a specialised microenvironment depends on the balance of enhancement signals and inhibitory signals. Specialised microenvironments involve the immune microenvironment, the matrix microenvironment, the cancer stem cell niche, the hypoxic microenvironment, the metabolic microenvironment, the acidic microenvironment, and the microbial microenvironment (right panel). TNFα, Tumor necrosis factor α. IFN-γ, Interferon-γ. IL-15/2/12/18/10, Interleukin-15/2/12/18/10. PGE2, Prostaglandin E2. IDO, Indoleamine 2,3-dioxygenase. TGF-β, Transforming growth factor-β. NKG2A/C/D, Natural killer group 2 member A/C/D. ROS, Reactive oxygen species. TIGIT: T-cell immunoglobulins and ITIM domain. CTLA-4, Cytotoxic T-lymphocyte antigen 4. PD-1, Programmed death-1. A2AR, A2A adenosine receptor. KIRs, Killer immunoglobulin-like receptors. NKp80: Natural cytotoxicity receptor 80. IL-15R, Interleukin 15 receptor. DNAM-1, DNAX accessory molecule 1. LFA-1, Lymphocyte function-associated antigen-1. ICAM-1, Intercellular adhesion molecule-1. MICA/B, MHC class I chain-related protein A/B. PD-L1, Programmed cell death ligand 1. HLA-C/E, Human leukocyte antigen C/E. CXCL9/10, Chemokine (C-X-C motif) ligand 9/10. Adapted from “The Key Role of Neuroinflammation in Neurodegenerative Diseases”, by BioRender.com (2022). Retrieved from https://app.biorender.com/biorender-templates