Molecular checkpoints controlling natural killer cell activation and their modulation for cancer immunotherapy
Experimental & Molecular Medicine 2017³â 49±Ç 3È£ p.4 ~ p.4
±ÇÇüÁØ(Kwon Hyung-Joon) - University of Ulsan College of Medicine Asan Medical Center Department of Biomedical Sciences
±è³ª¿µ(Kim Na-Young) - University of Ulsan College of Medicine Asan Medical Center Asan Institute for Life Sciences
±èÇå½Ä(Kim Hun-Sik) - University of Ulsan College of Medicine Asan Medical Center Department of Biomedical Sciences
Abstract
Natural killer (NK) cells have gained considerable attention as promising therapeutic tools for cancer therapy due to their innate selectivity against cancer cells over normal healthy cells. With an array of receptors evolved to sense cellular alterations, NK cells provide early protection against cancer cells by producing cytokines and chemokines and exerting direct cytolytic activity. These effector functions are governed by signals transmitted through multiple receptor?ligand interactions but are not achieved by engaging a single activating receptor on resting NK cells. Rather, they require the co-engagement of different activating receptors that use distinct signaling modules, due to a cell-intrinsic inhibition mechanism. The redundancy of synergizing receptors and the inhibition of NK cell function by a single class of inhibitory receptor suggest the presence of common checkpoints to control NK cell activation through different receptors. These molecular checkpoints would be therapeutically targeted to harness the power of NK cells against diverse cancer cells that express heterogeneous ligands for NK cell receptors. Recent advances in understanding the activation of NK cells have revealed promising candidates in this category. Targeting such molecular checkpoints will facilitate NK cell activation by lowering activation thresholds, thereby providing therapeutic strategies that optimize NK cell reactivity against cancer.
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KMID :
0620920170490030004
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À¯È¿¼º°á°ú(Recomendation)
There is an urgent need to improve cancer immunotherapy using NK cells; Current efforts for NK cell-based therapy have mainly relied on strategies that manipulate the function of inhibitory receptors.