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Human nk cells: surface receptors, inhibitory checkpoints, and translational applications

Cellular & Molecular Immunology 2019年第5期16卷 430-441页

作者： Simona Sivori Paola Vacca Genny Del Zotto Enrico Munari Maria Cristina Mingari Lorenzo Moretta Department of Experimental Medicine(DIMES)and Centre of Excellence for Biomedical Research(CEBR) University of GenoaGenoaItaly Department of Immunology IRCCS Bambino GesuChildren’s HospitalRomeItaly Department of Research and Diagnostics Istituto G.GasliniGenoaItaly Department of Diagnostics and Public Health University of VeronaVeronaItaly Department of Pathology Sacro Cuore Don CalabriaNegrarVRItaly UOC Immunologia IRCCS Ospedale Policlinico San Martino GenovaGenoaItaly

nk cells play important roles in innate defenses against viruses and in the control of tumor growth and *** regulation/induction of nk cell function is mediated by an array of activating or inhibitory surface *** humans,major activating receptors involved in target cell killing are the natural cytotoxicity receptors(NCRs)and *** receptors recognize ligands that are overexpressed or expressed de novo upon cell stress,viral infection,or tumor *** HLA-class I-specific inhibitory receptors,including KIRs recognizing HLA-class I allotypic determinants and CD94/nkG2A recognizing the class-Ib HLA-E,constitute a fail-safe mechanism to avoid unwanted nk-mediated damage to healthy *** receptors such as PD-1,primarily expressed by activated T lymphocytes,are important inhibitory checkpoints of immune responses that ensure T-cell ***-1 also may be expressed by nk cells in cancer *** PD-1 ligand(PD-L1)may be expressed by different tumors,PD-1/PD-L1 interactions inactivate both T and nk ***,the reliable evaluation of PD-L1 expression in tumors has become a major issue to select patients who may benefit from therapy with mAbs disrupting PD-1/PD-L1 ***,nkG2A was revealed to be an important checkpoint controlling both nk and T-cell *** most tumors express HLA-E,mAbs targeting nkG2A has been used alone or in combination with other therapeutic mAbs targeting PD-1 or tumor antigens(e.g.,EGFR),with encouraging *** translational value of nk cells and their receptors is evidenced by the extraordinary therapeutic success of haploidentical HSCT to cure otherwise fatal high-risk leukemias.

关键词： Human nk cells nk receptors Inhibitory checkpoints Immunotherapy

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