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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01999

NK cell dysfunction and checkpoint immunotherapy

  • 1Shenzhen Institutes of Advanced Technology (CAS), China
  • 2Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, China
  • 3CAS Key Laboratory of Innate Immunity and Chronic Disease, University of Science and Technology of China, China
  • 4Insititue of Immunology, School of Life Science, University of Science and Technology of China, China

NK cells play important roles in the innate immune responses against tumors. The effector function of NK cells relies on the integration of activating and inhibitory signals. Emerging checkpoint receptors and molecules are being revealed to mediate NK cell dysfunction in the tumor microenvironment. Inhibition of some NK cell surface checkpoint receptors has displayed the potential to reverse NK cell dysfunction in tumors, and to boost anti-tumor immunity, both in clinical trials (anti-KIR and anti-NKG2A), and in preclinical studies (e.g. anti-TIGIT, and anti-CD96). To fully exploit the potential of NK–based checkpoint immunotherapy, more understanding of the regional features of NK cells in the tumor microenvironment is required. This will provide valuable information regarding the dynamic nature of NK cell immune response against tumors, as well as novel checkpoints or pathways to be targeted. In this Review, we discuss recent advances in the understanding of NK cell dysfunction in tumors, as well as emerging strategies of NK –based checkpoint immunotherapy for tumors.

Keywords: inhibitory receptors, checkpoint blockade, Immune Evasion, Immune Tolerance, regional immunity

Received: 27 May 2019; Accepted: 07 Aug 2019.

Edited by:

Daniel Olive, Faculté de Médecine, Aix Marseille Université, France

Reviewed by:

Eric Vivier, INSERM U1104 Centre d'immunologie de Marseille-Luminy, France
Robin Parihar, Baylor College of Medicine, United States  

Copyright: © 2019 Bi and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Jiacheng Bi, Shenzhen Institutes of Advanced Technology (CAS), Shenzhen, Guangdong Province, China, jc.bi@siat.ac.cn
Prof. Zhigang Tian, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Division of Molecular Medicine, Hefei, 230026, Anhui Province, China, tzg@ustc.edu.cn