title: Expression regulation of co-inhibitory molecules on human natural killer cells in response to cytokine stimulations.
abstract: Co-inhibitory molecules have become the key targets in cancer immunotherapy with the strategy of blocking immune checkpoints to reverse the pathogenic regulation of T cells. However, their expression regulations in NK cells, the most important innate immune cells against tumor, remain largely undefined. In this study, we showed that the expressions of co-inhibitors on NK cells, including LAG-3, PD-1, and TIGIT, are differently regulated by cytokines IL-10, IL-12, IL-15, IFN-α, and TGF-β. Among the tested cytokines, IL-12 is the most powerful inducer of LAG-3, and TGF-β is the strongest suppresser of PD-1. Notably, the expression of these co-inhibitors responds to the time course of stimulus progressively. Together, these findings illustrated that the co-inhibitors on NK cells express differently in response to cytokine stimulations of IL-10, IL-12, IL-15, IFN-α, and TGF-β, providing an initial information on the expression regulation of co-inhibitors in human NK cells.
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Sun
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.forename: Weihua
authors.initials: W
authors.lastname: Xiao
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053765:Interleukin-12 Subunit p35 / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; C508609:IL10 protein, human; C508858:IL12A protein, human; C569274:IL15 protein, human; D016898:Interferon-alpha; D053765:Interleukin-12 Subunit p35; D019409:Interleukin-15; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic; C534712:TIGIT protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human
keywords: Co-inhibitory molecule; Cytokine; Gene regulation; IFN-α; IL; LAG-3; LAG-3-associated protein; LAP; MHC; NK cell; Natural killer cell; PD-1; T cell immunoglobulin and ITIM domain; TGF-β; TIGIT; interferon-α; interleukin; lymphocyte activation gene-3; major histocompatibility complex; natural killer cell; programmed death-1; tumor growth factor-β