PD-1 receptor deficiency enhances CD30+ Treg cell function in melanoma

Abstract Regulatory T (T reg ) cells are vital for immune suppression. The role of the coreceptor programmed cell death 1 receptor (PD-1) in T reg cell function is controversial. Here, we demonstrate that PD-1 deficiency enhances the function of T reg cells through expression of a compensatory network of coinhibitory receptors. CD30 has a central role within this network, driving the T reg cell suppressive function within the tumor microenvironment. Mechanistically, PD-1 deficiency enhances STAT5 signaling in T reg cells, which induces CD30 expression. These data indicate a role for PD-1 as a checkpoint that negatively controls CD30 expression in T reg cells to limit their suppressive function. Understanding the functional changes that PD-1 has on T reg cells might enable combination therapies with better treatment outcomes in cancer.