Assessment and enhancement of natural killer cell-mediated anti-tumor immunity in brain metastasis 4449

Abstract Description Uncontrolled proliferation of metastatic solid tumors accounts for most cancer-related deaths. Metastatic tumors in the brain exemplify several key difficulties associated with researching and treating metastatic disease, including poor tissue penetration by anti-neoplastic drugs and tight control of infiltrating immune cell function. Potentiation of brain-infiltrating effector immune cells represents a favorable strategy for the clinical management of brain metastasis. Natural killer (NK) cells have shown particular promise in this regard. Accumulating clinical and pre-clinical evidence supports a vital role for NK cells in anti-metastatic immunity and has prompted the rapid development of both NK cell engagers and adoptive NK cell transplants—both of which have entered clinical trials. Our work seeks to define NK cell anti-metastatic function in the brain and enhance NK cell-mediated control of brain metastasis. We observe that NK cells rapidly infiltrate metastatic brain lesions but fail to control metastatic outgrowth. scRNA-seq reveals phenotypic polarization in brain-infiltrating NK cells relative to those infiltrating other organs. We further demonstrate that cytokine treatment expands tumor-responsive populations of NK cells and ILC1s in the brain—improving tumor control. These findings will inform advances in cell-based therapies to improve metastatic control in the brain—with the end goal of rapid clinical translation in the adoptive NK cell therapy space. Funding Sources NIH 5R01CA237376 NIH T32-GM008620 CIRM EDUC4-12822 Topic Categories Neuroimmunology (NEUR)