CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向 p97-Npl4 相互作用抑制肿瘤 T(reg) 细胞发育以增强肿瘤免疫
英文原题：Targeting p97-Npl4 interaction inhibits tumor T(reg) cell development to enhance tumor immunity.
查看英文原题
Targeting p97-Npl4 interaction inhibits tumor T(reg) cell development to enhance tumor immunity.
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中文摘要
靶向肿瘤浸润性调节性T（TI-T reg）细胞是一种潜在的癌症治疗策略。ATP酶p97与辅因子（如Npl4）形成的复合物已被研究作为抗肿瘤药物靶点；然而，p97在免疫细胞或免疫治疗中是否具有功能尚不清楚。在此，我们展示溴化索那宗（thonzonium bromide）是p97与Npl4相互作用的抑制剂，并且该p97-Npl4复合物在TI-T reg细胞中具有关键功能。溴化索那宗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桥接，从而促进Stat3降解并支持TI-T reg细胞发育。总体而言，这项工作显示了p97-Npl4复合物在控制肿瘤中T reg-T H 17细胞平衡中的重要作用，并确定了免疫治疗的可能靶点。
展开英文摘要原文
Targeting tumor-infiltrating regulatory T (TI-T reg ) 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-T reg cells. Thonzonium bromide boosts antitumor immunity without affecting peripheral T reg cell homeostasis.
The p97-Npl4 complex bridges Stat3 with E3 ligases PDLIM2 and PDLIM5, thereby promoting Stat3 degradation and enabling TI-T reg cell development. Collectively, this work shows an important role for the p97-Npl4 complex in controlling T reg -T H 17 cell balance in tumors and identifies possible targets for immunotherapy.
论文信息
- 作者
- Nie P、Cao Z、Yu R、Dong C、Zhang W、Meng Y、Zhang H、Pan Y
- 第一作者单位
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.China
- 通讯作者单位
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai, China. zhouzhaocai@fudan.edu.cn.China
- 期刊
- Nature immunology2024 Sep
- 原文标识
- PubMed 39107403 · DOI 10.1038/s41590-024-01912-y