Human NK cells, their receptors and function

Abstract

NK cells are cytotoxic components of innate lymphoid cells (ILC) that provide a first line of defense against viral infections and contribute to control tumor growth and metastasis. Their function is finely regulated by an array of HLA‐specific and non‐HLA‐specific inhibitory and activating receptors which allow to discriminate between healthy and altered cells. Human NK cells gained a major attention in recent years because of the important progresses in understanding their biology and of some promising data in tumor therapy. In this review, we will outline well‐established issues of human NK cells and discuss some of the open questions, debates, and recent advances regarding their origin, differentiation, and tissue distribution. Newly defined NK cell specializations, including the impact of inhibitory checkpoints on their function, their crosstalk with other cell types, and the remarkable adaptive features acquired in response to certain virus infections will also be discussed.

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

“…Multiple cytotoxic receptors can activate NK cells: CD16 (FcγRIII), natural cytotoxicity receptors (NCRs; NKp30, NKp44, NKp46), C-type lectin-like receptors NKG2D (CD314), and CD94/NKG2C. Among these, CD16A is an activating receptor expressed on NK cells and macrophages, and binding of the Fc region induces ADCC of target cells ( 34 ). NK cell engagers are divided into tandem scFv-based bispecific killer cell engagers (BiKEs) and TAA-specific scFv fused to anti-CD16A, also referred to as trispecific killer cell engager (TriKE).…”

Recent Advances in the Diagnosis and Treatment of Natural Killer Cell Malignancies

“…Expression of the transcription regulators STAT5, NFIL3, NOTCH, PU.1, TCF1, RUNX3 and CBFB leads to NK lineage commitment [2]. NKcells are part of the innate immune system and are responsible for detection and killing of tumour or virally infected cells [3]. They are strategically located at mucosal surfaces, the skin and gut, and they circulate between the blood and bone marrow [3].…”

“…NKcells are part of the innate immune system and are responsible for detection and killing of tumour or virally infected cells [3]. They are strategically located at mucosal surfaces, the skin and gut, and they circulate between the blood and bone marrow [3]. The normal residency of NK-cells in these sites accounts for the predominant extranodal localization of malignancies arising from neoplastic NK-cells [4].…”

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

“…Except for CD16, activating receptors must be simultaneously crosslinked in pairs or combinations to elicit synergistic activation signals for NK cell function. 2 , 3 , 4 …”