Tailoring Natural Killer cell immunotherapy to the tumour microenvironment

•The solid tumour microenvironment suppresses NK cell functions and is a significant barrier to successful immunotherapy.•Elucidating immunosuppressive pathways employed by solid tumours is vital for the rational design of novel immunotherapies.•Nullifying tumour-induced immunosuppression will augment established immunotherapies, such as checkpoint blockade.•Converting inhibitory into activating receptors using CAR technology may furnish a novel approach for tumour immunotherapy.

Natural killer (NK) cells are cytotoxic and cytokine-secreting cells that can mediate potent anti-tumour activity. Accumulating evidence indicates that NK cell functions are severely compromised within the confines of the tumour microenvironment thus impairing the efficacy and development of NK cell-based therapies. Here we review the various cellular and molecular pathways that tumours have supplanted to evade NK cell surveillance. We highlight novel strategies designed to alleviate or circumvent the immunosuppressive conditions of the tumour microenvironment in order to emancipate NK cell function and stifle the inexorable growth and metastasis of malignant cells.