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Secreted PTEN binds PLXDC2 on macrophages to drive antitumor immunity and tumor suppression.
Zhang, Cheng; Ma, Hong-Ming; Wu, Shuai; Shen, Jia-Ming; Zhang, Na; Xu, Yi-Lu; Li, Cheng-Xiao; He, Ping; Ge, Meng-Kai; Chu, Xi-Li; Zhang, Yu-Xue; Zheng, Jun-Ke; Chen, Guo-Qiang; Shen, Shao-Ming.
Afiliación
  • Zhang C; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; School of Bas
  • Ma HM; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; Department of
  • Wu S; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Shen JM; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; Department of
  • Zhang N; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Xu YL; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Li CX; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • He P; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China.
  • Ge MK; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Chu XL; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Zhang YX; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Zheng JK; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai 200025, China.
  • Chen GQ; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; School of Bas
  • Shen SM; Institute of Aging & Tissue Regeneration, Stress and Cancer Research Unit of Chinese Academy of Medical Sciences (No.2019RU043), State Key Laboratory of Systems Medicine for Cancer, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200127, China; Department of
Dev Cell ; 2024 Aug 26.
Article en En | MEDLINE | ID: mdl-39197453
ABSTRACT
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 switches tumor-associated macrophages (TAMs) from the immunosuppressive to inflammatory phenotype, leading to enhanced activation of CD8+ T and natural killer cells. Importantly, PTEN treatment also enhances the therapeutic efficacy of anti-PD-1 treatment in mice and reverses the immune-suppressive phenotype of patient-derived primary TAMs. These data identify a cytokine-like role of PTEN in immune activation and tumor suppression and demonstrate the therapeutic potential for extracellular administration of PTEN in cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos