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

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.