TISSUE-SPECIFIC SPATIAL REGULATION OF INNATE IMMUNE CHECKPOINTS IN CANCER

Natural killer (NK) and innate lymphoid cells (ILCs) regulate tissue homeostasis and immune responses, by acting as early sensors of cellular stress and tissue dysfunction. Their functions are tightly controlled by regulatory circuits, often referred to as checkpoints, and are profoundly shaped by local environments. In cancer, tissue perturbations cause immune cell recruitment, spatial re-distribution, and accordant functional adaptations. Here, we discuss how tissue-specific cues regulate NK/ILC functions in cancer, and how local regulatory circuits shape their cellular states and effector programs. We address how targeting innate checkpoints could aid existing, and inform novel strategies for treating solid malignancies.