Deceleration of glycometabolism impedes IgG-producing B-cell-mediated tumor elimination by targeting SATB1

作者：Liu, Jiajing; Li, Yifan; Lu, Zhou; Gu, Jie; Liang, Yun; Huang, Enyu; Wang, Zhiming; Zhang, Hushan; Wang, Luman; Zhang, Dan; Yu, Hongxiu; Liu, Ronghua^*; Chu, Yiwei^*

来源：Immunology, 2019, 156(1): 56-68.

DOI：10.1111/imm.12998

• B cells
• metabolic disorder
• tumor immunology

B lymphocytes, known as antibody producers, mediate tumor cell destruction in the manner of antibody-dependent cell-mediated cytotoxicity; however, their anti-tumor function seems to be weakened during tumorigenesis, while the underlying mechanisms remain unclear. In this study, we found that IgG mediated anti-tumor effects, but IgG-producing B cells decreased in various tumors. Considering the underlying mechanism, glycometabolism was noteworthy. We found that tumor-infiltrating B cells were glucose-starved and accompanied by a deceleration of glycometabolism. Both inhibition of glycometabolism and deprivation of glucose through tumor cells, or glucose-free treatment, reduced the differentiation of B cells into IgG-producing cells. In this process, special AT-rich sequence-binding protein-1 (SATB1) was significantly silenced in B cells. Down-regulating SATB1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 (STAT6) to the promoter of germline C gene, subsequently resulting in fewer B cells producing IgG. Our findings provide the first evidence that glycometabolic inhibition by tumorigenesis suppresses differentiation of B cells into IgG-producing cells, and altering glycometabolism may be promising in improving the anti-tumor effect of B cells.

• 出版日期2019-1
• 单位复旦大学