Thymic NK-Cells and Their Potential in Cancer Immunotherapy

Abstract

Caitlyn Forbes,1 Stefan Nierkens,1,2,* Annelisa M Cornel1,2,* 1Princess Máxima Center for Pediatric Oncology, Utrecht University, Utrecht, the Netherlands; 2Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands*These authors contributed equally to this workCorrespondence: Stefan Nierkens, Utrecht University, Heidelberglaan 25, Utrecht, 3584 CS, the Netherlands, Tel [phone], Fax [phone], Email [email protected]: Natural killer (NK)-cells are innate immune cells with potent anti-tumor capacity, capable of recognizing target cells without prior exposure. For this reason, NK-cells are recognized as a useful source of cell therapy. Although most NK-cells are derived from the bone marrow (BM), a separate developmental pathway in the thymus also exists, producing so-called thymic NK-cells. Unlike conventional NK-cells, thymic NK (tNK)-cells have a combined capacity for cytokine production and a natural ability to kill tumor cells in the presence of NK-cell receptor stimulatory ligands. Furthermore, tNK-cells are reported to express CD3 subunits intracellularly, without the presence of a rearranged T-cell receptor (TCR). This unique feature may enable harnessing of these cells with a TCR to combine NK- and T-cell effector properties in one cell type. The development, phenotype, and function of tNK-cells, and potential as a cell therapy is, however, poorly explored. In this review, we provide an overview of current literature on both murine and human tNK-cells in comparison to conventional BM-derived NK-cells, and discuss the potential applications of this cellular subset in the context of cancer immunotherapy.Keywords: tumor immunogenicity, cancer immunotherapy, gene engineering, T-cell receptor

Keywords

• tumor immunogenicity
• cancer immunotherapy
• gene engineering
• t-cell receptor