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

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年6月2日

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  • Jing Xuan Lim,
  • Tegan McTaggart,
  • Seol Kyoung Jung,
  • Katie J. Smith,
  • Gillian Hulme,
  • Stephanie Laba,
  • Yun Qi Ng,
  • Amelia Williams,
  • Rafiqul Hussain,
  • Jonathan Coxhead,
  • Ioana Cosgarea,
  • Catherine Arden,
  • Jérémie Nsengimana,
  • Penny Lovat,
  • Graham Anderson,
  • Hong-Wei Sun,
  • Arian Laurence,
  • Shoba Amarnath

摘要

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.