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SCI 28 August 2024 Targeting p97-Npl4 interaction inhibits tumor Tregcell development to enhance tumor immunity (nature immunology; if=27.7) Nie P, Cao Z, Yu R, Dong C, Zhang W, Meng Y, Zhang H, Pan Y, Tong Z, Jiang X, Wang S, Zhu M, Han Y, Wang W, Zhang Y, Tan L, Li C, Xu Y, An L, Li B, Jiao S, Zhou Z. Correspondence: jiaoshi@fudan.edu.cn; zhouzhaocai@fudan.edu.cn 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
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