NK cell responses in immunotherapy: Novel targets and applications

The aim of cancer immunotherapy is to favorably alter the immune response to tumors, with the goal of inducing tumor regression and ultimately durable clinical responses. Amongst immune cells, natural killer (NK) cells possess unique capabilities that make them of great interest as key effectors of immunotherapy. Initially described over 30 years ago with the ability to spontaneously kill tumor cells, NK cells were later shown to recognize and eliminate tumor cells with low or absent major histocompatibility class I (MHC I) expression, otherwise known as the "missing self" hypothesis (Karre et al. (Nature 319:675-678, 1986); Ljunggren and Karre, (Immunol. Today 11:237-44., 1990)). Because of such properties, NK cells have been vigorously studied in the context of cancer immunotherapy. In more recent years, increasing evidence has shown that NK cells have more adaptive immune features than previously thought (O’Leary et al. (Nat. Immunol. 7:507-16, 2006); Nabekura and Lanier (J. Exp. Med. 211:2455-65, 2014), Sun et al. (Eur. J. Immunol. 39:2059-64., 2009)), perhaps making them even more attractive as tools to optimize the antitumor immune response. Herein, we review some of the basic biology of human NK cells and explore their ongoing therapeutic development and application in cancer immunotherapy.