Spotlight on Natural Killer Cells in Immuno-Oncology

Dear Colleagues,

Although treatment strategies for cancer have been steadily advancing, we still lack comprehensive and durable treatment modalities to successfully prevent, treat, or cure cancer. In recent years, we have seen approvals of cellular therapies for clinical use; in coming years, we expect to see several others, such as novel natural killer cell (NK), chimeric antigen receptor T-cell (Car-T), tumor infiltrating lymphocyte (TIL), and NK-Car therapies, approved as clinical agents. The ability of NK cells to target cancer stem cells and poorly differentiated tumors that lack adequate levels of MHC class I has afforded primary NK cells a very unique and indispensable role in cancer immunotherapy. It is also known that cancer patients have dysfunctional NK cells in addition to decreased numbers; indeed, inactivation of NK function has been shown to occur at the pre-neoplastic stages of tumorigenesis, making these cells one of the most important immune effectors responsible for the prevention of cancer. However, limitations in the expansion of NK cells to sufficient numbers, the inability to obtain adequate functional NK cells from different cellular sources, and a lack of understanding of the immunobiology of these cells have traditionally hampered progress in the field of NK cell immunotherapy. Therefore, strategies should be designed to allow maintenance of good NK expansion and function in cancer patients since NK cells are known to limit the expansion of Tumor-Associated Macrophages (TAMs), Tregs, and MDSCs in addition to the removal of CSCs/undifferentiated tumors, which are the hallmarks of aggressive tumors. Large numbers of functionally competent NK cells can be combined with other immunotherapeutic strategies such as oncolytic viruses, ADCC inducing antibodies, check point inhibitors, CAR-T, CAR-NK, TIL, and chemotherapeutic and radiotherapeutic strategies for the ultimate goal of tumor eradication.

This collection of comprehensive reviews and original articles should highlight the significant advances made in the field of NK cells, and potential new directions which should help advance the field and bring us to the finish line.

Prof. Dr. Anahid Jewett
Dr. Kawaljit Kaur
Guest Editors

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• natural killer (NK) cells
• cancer stem cells (CSCs)
• poorly differentiated tumors
• differentiation
• aggressive tumors
• suppressor cells