Natural killer (NK) cells, immune cells with an innate ability to recognize and eliminate cancer cells, have emerged as attractive effectors in immunotherapy, owing in large part to their ability to target cancers based on MHC ligand mismatch, thus representing a source of potentially allogeneic immune cells, and a safer alternative to T cells. As such, various approaches aimed at exploiting NK cells for immunotherapy have been in development. These approaches have leveraged genetic engineering as a tool to regulate NK cell activation in terms of controlling their anti-tumor function, metabolism and persistence, and have shown promise as anti-cancer therapies. However, targeting complex cancers such as aggressive solid tumors remains a challenge due to profound immunosuppression in the microenvironment of such cancers, which dampens not only NK cell, but also other immune effector responses. In this talk, we discuss opportunities for NK cells in immunotherapy, including novel genetic engineering approaches and therapeutic modulation strategies aimed at enhancing NK cell immune responses, with the ultimate goal to effectively and durably targeting currently uncurable cancers.

Learning Objectives:

1. Understand and summarize how natural killer cells recognize and eliminate cancers.

2. Describe methods to enhance and regulate natural killer cell activity in tumors in the context of immunotherapy.

3. Explain challenges in targeting the tumor microenvironment in cancer.