近日，英国纽卡斯尔大学教授Shoba Amarnath及其团队报道了PD-1受体缺乏增强黑色素瘤中CD30⁺ T_reg细胞的功能。相关论文于2025年6月2日发表在《自然—免疫学》杂志上。

研究人员证明PD-1缺乏通过共抑制受体代偿网络的表达增强T_reg细胞的功能。CD30在这个网络中起核心作用，在肿瘤微环境中驱动T_reg细胞抑制功能。在机制上，PD-1缺失增强T_reg细胞中的STAT5信号传导，从而诱导CD30表达。这些数据表明，PD-1作为检查点的作用是负性地控制T_reg细胞中的CD30表达，以限制其抑制功能。了解PD-1对T_reg细胞的功能变化可能会使联合治疗在癌症中获得更好的治疗效果。

据了解，调节性T （T_reg）细胞对免疫抑制至关重要。辅助受体程序性细胞死亡1受体（PD-1）在T_reg细胞功能中的作用尚存争议。

附：英文原文

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

Author: 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, Jrmie, Lovat, Penny, Anderson, Graham, Sun, Hong-Wei, Laurence, Arian, Amarnath, Shoba

Issue&Volume: 2025-06-02

Abstract: 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.

DOI: 10.1038/s41590-025-02172-0

Source: https://www.nature.com/articles/s41590-025-02172-0