Exploring the contributions of 2B4 and CD48 to natural killer cell activation and cancer killing

Abstract

Natural killer (NK) cells are known mediators of immunosurveillance and anti-cancer activity. They prevent cancer growth and relapse and are increasingly used for cancer immunotherapy. NK cells distinguish non-cancerous “self” cells through recognition of human leukocyte antigen (HLA) using polymorphic inhibitory receptors such as killer immunoglobulin- like receptors (KIRs) in a process trained by NK cell ‘education’. NK cells identify malignant cells through lack of HLA, and co-expressed germline encoded receptors that deliver concurrent activating and inhibitory signals. NK cell function differs within and between individuals due to receptor expression diversity. They can be expanded virtually limitlessly, and adoptive transfer across allogeneic barriers is safe and feasible. NK cell subpopulations differ in strength of their anti-cancer function, but current therapies have not yet taken advantage of this by selecting, engineering, or enhancing key features during NK cell expansion and preparation. Using high parameter flow cytometry, this project investigated the prominent and complex NK cell receptor-ligand pair, 2B4 and CD48. The role of 2B4-CD48 self NK cell interactions, and how this influences subsequent responsiveness towards cancer cells, is not well understood. Understanding this might help inform the most potent NK cell that can be selected and leveraged to harness this anti- cancer activity. With this knowledge, we can inform precise application of NK cell subsets, which can inform the development of NK cells as precise and off-the-shelf immunotherapies against leukemia, that can be expanded to treat other cancers.