Restriction of PD-1 function by cis-PD-L1/CD80 interactions is required for optimal T cell responses
Menée in vitro et à l'aide d'un modèle murin, cette étude met en évidence la nécessité d'interactions cis entre les protéines CD80 et PD-L1 des cellules présentatrices d'antigènes pour restreindre la fonction de PD-1 et optimiser la réponse antitumorale des lymphocytes T
Targeted blockade of PD-1 using checkpoint inhibitor immunotherapies can activate T cells to destroy tumors. PD-1 is believed to function mainly at the effector but not in the activation phase of T cell responses, yet how PD-1 function is restricted at the activation stage is currently unknown. Here we demonstrate that CD80 interacts with PD-L1 in cis on antigen presenting cells (APCs) to disrupt PD-L1/PD-1 binding. Subsequently, PD-L1 cannot engage PD-1 to inhibit T cell activation when APCs express substantial amounts of CD80. Using knock-in mice where cis-PD-L1/CD80 interactions do not occur, tumor immunity and autoimmune responses were greatly attenuated by PD-1. These findings indicate that CD80 on APCs limits the PD-1 co-inhibitory signal, while promoting CD28-mediated co-stimulation, and highlights critical components for induction of optimal immune responses.