title: Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3.
abstract: 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.
authors.affiliation: Department of Immunology, Nankai University School of Medicine and Key Laboratory of Bioactive Materials, Ministry of Education, Nankai University, Tianjin, People's Republic of China.
authors.forename: Zhuohan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qiaofei
authors.initials: Q
authors.lastname: Liu
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Che
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.forename: Lingyun
authors.initials: L
authors.lastname: Dai
authors.forename: Bin
authors.initials: B
authors.lastname: Zeng
authors.forename: Guohui
authors.initials: G
authors.lastname: Jiao
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.forename: Yinyan
authors.initials: Y
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rongcun
authors.initials: R
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D047468:Immunoprecipitation; D007167:Immunotherapy; D018374:LLC-PK1 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy; D011770:Pyruvate Kinase / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000276:immunology / Q000378:metabolism*; D013552:Swine
chemical_list: C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000255:Adenosine Triphosphate; D011770:Pyruvate Kinase