Antigen Presentation by Dendritic Cells in Tumors Is Disrupted by Altered Metabolism that Involves Pyruvate Kinase M2 and Its Interaction with SOCS3

作者：Zhang, Zhuohan; Liu, Qiaofei; Che, Yongzhe; Yuan, Xin; Dai, Lingyun; Zeng, Bin; Jiao, Guohui; Zhang, Yin; Wu, Xue; Yu, Yinyan; Zhang, Yuan; Yang, Rongcun^*

来源：Cancer Research, 2010, 70(1): 89-98.

DOI：10.1158/0008-5472.CAN-09-2970

• PHYSIOLOGICAL NEGATIVE REGULATOR
• SH2 DOMAIN
• SIGNAL-TRANSDUCTION
• IMMUNE-RESPONSES
• CYTOKINE
• PROTEIN
• SUPPRESSOR
• BINDING
• GRANULOPOIESIS
• PAPILLOMAVIRUS

Dendritic cell (DC) function is negatively affected by tumors and tumor-derived factors, but little is known about the underlying mechanisms. Here, we show that intracellular SOCS3 in DCs binds to pyruvate kinase type M2 (M2-PK), which plays a critical role in ATP production through glycolysis. The interaction of SOCS3 with M2-PK reduced ATP production and impaired DC-based immunotherapy against tumors. Thus, SOCS3, which has been shown to be upregulated by tumor-derived factors, interacts with M2-PK to decrease ATP production, causing DC dysfunction. These dysfunctional DCs have a reduced ability to present antigens. Alteration of DC metabolism mediated by SOCS3 represents a novel mechanism for DC dysfunction in the tumor microenvironment. Cancer Res; 70(1); 89-98.

• 出版日期2010-1-1
• 单位南开大学