PD-1 receptor deficiency enhances CD30+ Treg cell function in melanoma
Jing Xuan Lim, Tegan McTaggart, Seol Kyoung Jung, Katie J Smith, Gillian Hulme, Stephanie Laba, Yin‐Shan Ng, Amelia Williams, Rafiqul Hussain, Jonathan Coxhead, Ioana Cosgarea, Catherine Arden, Jérémie Nsengimana, Penny E. Lovat, Graham Anderson, Hong‐Wei Sun, Arian Laurence, Shoba Amarnath
Abstract
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.