Emerging Insights into Natural Killer Cell Immunity in Infection and Cancer

Dear Colleagues,

Notable attention is deliberated toward understanding natural killer (NK) cells which are the first line of defense against tumor development and viral infections. NK cells, a subset of innate lymphoid cells (ILCs) derived from common lymphocyte progenitors, are potent naturally cytotoxic cells and are known to produce inflammatory cytokines and chemokines. NK cell activity is governed by the collective signals received from cell-surface-activating and inhibitory receptors that orchestrate the delicate balance between immune responses and self-tolerance. Originally discovered as an innate lymphocyte, the entirely novel functions and characteristics of NK cells are just beginning to be unveiled. Recent research has revealed that under certain viral infections or combination of cytokines, stimulation NK cells can exhibit memory or memory-like responses, which were traditionally attributed only to the adaptive immune system.

For decades, scientists have investigated NK cell-based immunotherapies against cancer due to their rapid killing power without any prior sensitization. Initial data from the on-going clinical trials have demonstrated outstanding safety of NK cell infusion, even in the allogeneic setting. Hematopoietic tumor cells often express uniform antigens, making them suitable targets for generating chimeric antigen receptor (CAR) NK cells, such as CD19-CAR NK cells. Additionally, NK cells pose a lower risk of cytokine release syndrome (CRS) compared to CAR T cells. Despite considerable progression in immunotherapies, several challenges must be overcome, such as limited in vivo persistence, limited infiltration into solid tumors and immunoediting of the tumor to evade NK cells. NK cell-derived extracellular vesicles (NK-EVs) containing cytotoxic proteins, cytokines and miRNAs show promise as cancer immunotherapy. Researchers are also actively exploring NK cell-based immunotherapy for treating various viral infections. Ongoing clinical efforts focus on using NK cell products to combat viruses such as HIV, cytomegalovirus (CMV), influenza, BK virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
We invite submissions of research articles, reviews and communications that fall under one of the following umbrellas of research areas:

• NK cell-directed approaches, including CAR NK cells, to control tumors;
• NK cell-derived extracellular vesicles and tumor targeting;
• Memory-like NK cells for tumor and infection control;
• Approaches to activate and expand NK cells for effective anti-tumor and anti-viral immunity;
• Tumor microenvironment and NK cells.

Dr. Sumit Sen Santara
Dr. Engin Berber
Dr. Weshely Kujur
Dr. Sachin Mulik
Guest Editors

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• CAR NK cells
• cancer immunotherapy
• cell therapy
• viral infection
• memory NK cells
• NK cell targeted therapies
• NK-immune cell crosstalk
• exosomes