Thymic expression of immune checkpoint molecules and their implication for response to immunotherapies

The thymus is responsible for generating a diverse T cell repertoire that is tolerant to self, but capable of responding to various immunologic insults, including cancer. Checkpoint blockade has changed the face of cancer treatment by targeting inhibitory molecules, which are known to regulate peripheral T cell responses. However, these inhibitory molecules and their ligands are expressed during T cell development in the thymus. In this review, we describe the underappreciated role of checkpoint molecule expression during the formation of the T cell repertoire and detail the importance of inhibitory molecules in regulating T cell lineage commitment. Understanding how these molecules function in the thymus may inform therapeutic strategies for better patient outcomes.