Lim Jing Xuan, McTaggart Tegan, Jung Seol Kyoung, Smith Katie J, Hulme Gillian, Laba Stephanie, Ng Yun Qi, Williams Amelia, Hussain Rafiqul, Coxhead Jonathan, Cosgarea Ioana, Arden Catherine, Nsengimana Jérémie, Lovat Penny, Anderson Graham, Sun Hong-Wei, Laurence Arian, Amarnath Shoba
Biosciences Institute, Newcastle University, Newcastle University, Newcastle upon Tyne, UK.
NIHR, Biomedical Research Centre, Newcastle University, Newcastle upon Tyne, UK.
Nat Immunol. 2025 Jun 2. doi: 10.1038/s41590-025-02172-0.
Regulatory T (T) cells are vital for immune suppression. The role of the coreceptor programmed cell death 1 receptor (PD-1) in T cell function is controversial. Here, we demonstrate that PD-1 deficiency enhances the function of T cells through expression of a compensatory network of coinhibitory receptors. CD30 has a central role within this network, driving the T cell suppressive function within the tumor microenvironment. Mechanistically, PD-1 deficiency enhances STAT5 signaling in T cells, which induces CD30 expression. These data indicate a role for PD-1 as a checkpoint that negatively controls CD30 expression in T cells to limit their suppressive function. Understanding the functional changes that PD-1 has on T cells might enable combination therapies with better treatment outcomes in cancer.
调节性T（Treg）细胞对免疫抑制至关重要。共受体程序性细胞死亡1受体（PD-1）在T细胞功能中的作用存在争议。在此，我们证明PD-1缺陷通过共抑制受体补偿网络的表达增强T细胞功能。CD30在该网络中起核心作用，驱动肿瘤微环境内的T细胞抑制功能。机制上，PD-1缺陷增强T细胞中的STAT5信号传导，从而诱导CD30表达。这些数据表明PD-1作为一个检查点，负向控制T细胞中CD30的表达以限制其抑制功能。了解PD-1对T细胞的功能变化可能有助于开发联合疗法，在癌症治疗中取得更好的治疗效果。
