LAG-3, TIM-3, and TIGIT: Distinct functions in immune regulation

LAG-3, TIM-3, and TIGIT comprise the next generation of immune checkpoint receptors being harnessed in the clinic. Although initially studied for their roles in restraining T cell responses, intense investigation over the last several years has started to pinpoint the unique functions of these molecules in other immune cell types. Understanding the distinct processes that these receptors regulate across immune cells and tissues will inform the clinical development and application of therapies that either antagonize or agonize these receptors, as well as the profile of potential tissue toxicity associated with their targeting. Here, we discuss the distinct functions of LAG-3, TIM-3, and TIGIT, including their contributions to the regulation of immune cells beyond T cells, their roles in disease, and the implications for their targeting in the clinic.