复旦大学周兆才、焦石小组发现，靶向p97-Npl4相互作用抑制肿瘤T_reg细胞发育，增强肿瘤免疫。相关论文于2024年8月6日发表在《自然—免疫学》杂志上。

该课题组研究人员证明了溴化硫铵是p97和Npl4相互作用的抑制剂，并且这种p97 - Npl4复合物在TI-T_reg细胞中具有关键功能。溴唑铵增强抗肿瘤免疫而不影响外周T_reg细胞稳态。p97-Npl4复合物将Stat3与E3连接酶PDLIM2和PDLIM5连接起来，从而促进Stat3降解并使TI-T_reg细胞发育。

总的来说，这项工作显示了p97-Npl4复合物在控制肿瘤中T_reg-TH17细胞平衡中的重要作用，并确定了免疫治疗的可能靶点。

研究人员表示，靶向肿瘤浸润调节性T细胞(TI-T_reg)是一种潜在的癌症治疗策略。ATP酶p97与辅助因子(如Npl4)的复合物已被研究作为抗肿瘤药物的靶点。然而，p97是否在免疫细胞或免疫治疗中起作用尚不清楚。

附：英文原文

Title: Targeting p97–Npl4 interaction inhibits tumor Treg cell development to enhance tumor immunity

Author: Nie, Pingping, Cao, Zhifa, Yu, Ruixian, Dong, Chao, Zhang, Weihong, Meng, Yan, Zhang, Hui, Pan, Yu, Tong, Zhenzhu, Jiang, Xiaoya, Wang, Shilong, Zhu, Mengwen, Han, Yi, Wang, Wenjia, Zhang, Yiming, Tan, Lijie, Li, Chuanchuan, Xu, Yuanzhi, An, Liwei, Li, Bin, Jiao, Shi, Zhou, Zhaocai

Issue&Volume: 2024-08-06

Abstract: Targeting tumor-infiltrating regulatory T (TI-Treg) cells is a potential strategy for cancer therapy. The ATPase p97 in complex with cofactors (such as Npl4) has been investigated as an antitumor drug target; however, it is unclear whether p97 has a function in immune cells or immunotherapy. Here we show that thonzonium bromide is an inhibitor of the interaction of p97 and Npl4 and that this p97–Npl4 complex has a critical function in TI-Treg cells. Thonzonium bromide boosts antitumor immunity without affecting peripheral Treg cell homeostasis. The p97–Npl4 complex bridges Stat3 with E3 ligases PDLIM2 and PDLIM5, thereby promoting Stat3 degradation and enabling TI-Treg cell development. Collectively, this work shows an important role for the p97–Npl4 complex in controlling Treg–TH17 cell balance in tumors and identifies possible targets for immunotherapy.

DOI: 10.1038/s41590-024-01912-y

Source: https://www.nature.com/articles/s41590-024-01912-y