Immunotherapy has advanced tremendously in the past decade and cellular products are now being leveraged efficiently in a number of settings. Targeted therapeutic NK cell interventions and allogeneic NK cell products, in particular, hold a great deal of promise due to their ability to quickly kill tumor cells without graft versus host disease (GVHD) effects, as seen with T cells. This grant focuses on clinical implementation of novel NK targeted therapeutics and third-party NK cell products in a variety of cancer settings. An overarching hypothesis of this PPG is that successful tumor control by NK cells is mediated not only through direct cytolytic activity but also through recruitment of other immune components and interactions with the tumor microenvironment (TME). To that end, Core C will provide seamless sample processing and state-of-the-art assays to best inform the projects on how NK cell interventions and NK cell products perform, alter the immune landscape, and interact with the TME. The Core integrates the processing, storage/annotation, distribution, and analytic capabilities of the Translational Therapy Laboratory, an NCI funded Cancer Center Support Grant shared resource, with a number of novel techniques to gain deep understanding of NK cell biology, the immune landscape influencing and resulting from NK cell intervention, and the tumor microenvironment the NK cell interventions must operate in. Mass cytometry, CyTOF, will be used to phenotypically evaluate NK cells and immune reconstitution at a high level of detail. The CODEX platform will be leveraged to maximize histologic analysis of the TME, and a variety of flow cytometric and imaging-based assays will be used to determine NK cell function prior to and after patient treatment. Assays will be carried out equally across all projects to determine differences in pharmacokinetic and pharmacodynamic profiles of each of the products so they can be fairly compared to each other and inform project leaders on how to best implement NK cell immunotherapeutic interventions. Uniform, high-quality data generated in these studies will be integrated with clinical outcomes, in collaboration with Cores A and B, and will be made available to all of the projects in order to maximize synergy and limit variation generated by having different laboratories carry out assays for individual projects.