PD-1 receptor deficiency enhances CD30+ Treg cell function in melanoma.
Lim JX., McTaggart T., Jung SK., Smith KJ., Hulme G., Laba S., Ng YQ., Williams A., Hussain R., Coxhead J., Cosgarea I., Arden C., Nsengimana J., Lovat P., Anderson G., Sun H-W., Laurence A., Amarnath S.
Regulatory T (Treg) cells are vital for immune suppression. The role of the coreceptor programmed cell death 1 receptor (PD-1) in Treg cell function is controversial. Here, we demonstrate that PD-1 deficiency enhances the function of Treg cells through expression of a compensatory network of coinhibitory receptors. CD30 has a central role within this network, driving the Treg cell suppressive function within the tumor microenvironment. Mechanistically, PD-1 deficiency enhances STAT5 signaling in Treg cells, which induces CD30 expression. These data indicate a role for PD-1 as a checkpoint that negatively controls CD30 expression in Treg cells to limit their suppressive function. Understanding the functional changes that PD-1 has on Treg cells might enable combination therapies with better treatment outcomes in cancer.