Key Activating and Inhibitory Ligands Involved in the Mobilization of Natural Killer Cells for Cancer Immunotherapies

Immunotargets Ther. 2021 Nov 1:10:387-407. doi: 10.2147/ITT.S306109. eCollection 2021.

Abstract

Natural killer (NK) cells are the most potent arm of the innate immune system and play an important role in immunity, alloimmunity, autoimmunity, and cancer. NK cells recognize "altered-self" cells due to oncogenic transformation or stress due to viral infection and target to kill them. The effector functions of NK cells depend on the interaction of the activating and inhibitory receptors on their surface with their cognate ligand expressed on the target cells. These activating and inhibitory receptors interact with major histocompatibility complex I (MHC I) expressed on the target cells and make decisions to mount an immune response. NK cell immune response includes cytolytic activity and secretion of cytokines to help with the ongoing immune response. The advancement of our knowledge on the expression of inhibitory and activating molecules led us to exploit these molecules in the treatment of cancer. This review discusses the importance of activating and inhibitory receptors on NK cells and their clinical importance in cancer immunotherapy.

Keywords: activating and inhibitory receptors; cancer; innate immune system; natural killer cells; oncogenic transformation.

Publication types

  • Review

Grants and funding

GL received grants from the Department of Biotechnology (Grants numbers, BT/PR15533/MED/30/1616/2015; BT/PR14156/BRB/10/1515/2016), Swarna Jayanti Fellowship (DST/SJF/LSA-01/2017-18), from Department of Science and Technology, and Science and Engineering Research Board (EMR/2016/007108), Ministry of Science and Technology, Government of India. SK received a Senior Research Fellowship from the Council of Scientific and Industrial Research (CSIR), Government of India. PP received a Senior Research Fellowship from the Department of Biotechnology (DBT), Government of India.