Chapter 18 - New therapeutic modalities in breast cancer by targeting NK cell inhibitory and activating receptors

Abstract

Since the discovery of natural killer cells in 1975, immunotherapies targeting the potent cytolytic activity and robust surveillance of the innate immune system have increased significantly. Many studies have explored the crucial role of NK cells in various cancers; however, the literature exploring the role of NK cells in breast cancer is limited. Despite the efficacy of conventional therapies in breast cancer, innate and induced resistances persist. Treatment strategies and resistance to such therapies vary across breast cancer subtypes, including the Luminal A, Luminal B, HER2-enriched, and triple-negative/basal-like subtypes. Here, we delineate the various potential signaling cross-talk pathways between NK cells and breast cancer. These pathways include, but are not limited to, the following: (i) NK cell activating receptors (e.g., NKG2D, DNAM1, and CD16), (ii) NK cell inhibitory receptors (e.g., NKG2A), and (iii) checkpoint inhibitors (e.g., PD-1). The stimulation of activating receptors or the disruption of inhibiting signaling with various postulated combination therapies may be key to overcoming resistance and unlocking the power of NK cell immunotherapy against breast tumors. This review provides significant support for targeting the NK cell activating or inhibitory receptors to activate the antitumor activities of NK cell-based therapies in breast cancer.