Premium
Deceleration of glycometabolism impedes IgG‐producing B‐cell‐mediated tumor elimination by targeting SATB 1
Author(s) -
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
Publication year - 2019
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12998
Subject(s) - carcinogenesis , biology , antibody , stat protein , cancer research , cytotoxicity , transcription (linguistics) , transcription factor , microbiology and biotechnology , stat3 , immunology , gene , biochemistry , signal transduction , in vitro , linguistics , philosophy
Summary 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 ( SATB 1) was significantly silenced in B cells. Down‐regulating SATB 1 by inhibiting glycometabolism or RNA interference reduced the binding of signal transducer and activator of transcription 6 ( STAT 6) to the promoter of germline C γ 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.