PD-1, BTLA and TIGIT as therapeutic targets for rheumatic disease.

Abstract

Immune-checkpoint molecules have essential roles in regulating immune responses, which maintain the delicate balance between physiological immune reactions and autoimmunity. The clinical success of immune checkpoint blockade for cancer therapy, and the occurrence of immune-related adverse events during cancer immunotherapy, highlight the profound effect of modulating these receptors on both tumour-specific and 'self'-specific responses. As a result, interest in exploring how these molecules can be targeted to treat autoimmune and rheumatological diseases is expanding. Targeting of the immune-checkpoint molecules PD-1, B and T lymphocyte attenuator (BTLA) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) to induce immune tolerance has shown therapeutic promise in pre-clinical models and, in some instances, clinical trials. A comprehensive understanding of how these receptors function in various immune cell populations, particularly T cells, and across different diseases is crucial for the successful translation of these findings to clinical applications.