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.

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.