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Secreted PTEN binds PLXDC2 on macrophages to drive antitumor immunity and tumor suppression

Developmental Cell. 2024-08; 
Cheng Zhang , Hong-Ming Ma , Shuai Wu , Jia-Ming Shen , Na Zhang , Yi-Lu Xu , Cheng-Xiao Li , Ping He , Meng-Kai Ge , Xi-Li Chu , Yu-Xue Zhang , Jun-Ke Zheng , Guo-Qiang Chen , Shao-Ming Shen
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摘要

Loss of phosphatase and tensin homolog (PTEN) has been linked to an immunosuppressive tumor microenvironment, but its underlying mechanisms remain largely enigmatic. Here, we report that PTEN can be secreted by the transmembrane emp24 domain-containing protein 10 (TMED10)-channeled protein secretion pathway. Inhibiting PTEN secretion from tumor cells contributes to immunosuppression and impairs the tumor-suppressive role of PTEN, while intratumoral injection of PTEN protein promotes antitumor immunity and suppresses tumor growth in mice. Mechanistically, extracellular PTEN binds to the plexin domain-containing protein 2 (PLXDC2) on macrophages, triggering subsequent activation of JAK2-STAT1 signaling, which swi... More

关键词

JAK2; PLXDC2; PTEN; TMED10; antitumor immunity; macrophages; unconventional protein secretion.