Unknown

Dataset Information

0

Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer.


ABSTRACT: Myeloid-derived suppressor cells (MDSCs) inhibit anti-tumor immunity. Aerobic glycolysis is a hallmark of cancer. However, the link between MDSCs and glycolysis is unknown in patients with triple-negative breast cancer (TNBC). Here, we detect abundant glycolytic activities in human TNBC. In two TNBC mouse models, 4T1 and Py8119, glycolysis restriction inhibits tumor granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) expression and reduces MDSCs. These are accompanied with enhanced T cell immunity, reduced tumor growth and metastasis, and prolonged mouse survival. Mechanistically, glycolysis restriction represses the expression of a specific CCAAT/enhancer-binding protein beta (CEBPB) isoform, liver-enriched activator protein (LAP), via the AMP-activated protein kinase (AMPK)-ULK1 and autophagy pathways, whereas LAP controls G-CSF and GM-CSF expression to support MDSC development. Glycolytic signatures that include lactate dehydrogenase A correlate with high MDSCs and low T cells, and are associated with poor human TNBC outcome. Collectively, tumor glycolysis orchestrates a molecular network of the AMPK-ULK1, autophagy, and CEBPB pathways to affect MDSCs and maintain tumor immunosuppression.

SUBMITTER: Li W 

PROVIDER: S-EPMC6238219 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Aerobic Glycolysis Controls Myeloid-Derived Suppressor Cells and Tumor Immunity via a Specific CEBPB Isoform in Triple-Negative Breast Cancer.

Li Wei W   Tanikawa Takashi T   Kryczek Ilona I   Xia Houjun H   Li Gaopeng G   Wu Ke K   Wei Shuang S   Zhao Lili L   Vatan Linda L   Wen Bo B   Shu Pan P   Sun Duxin D   Kleer Celina C   Wicha Max M   Sabel Michael M   Tao Kaixiong K   Wang Guobin G   Zou Weiping W  

Cell metabolism 20180524 1


Myeloid-derived suppressor cells (MDSCs) inhibit anti-tumor immunity. Aerobic glycolysis is a hallmark of cancer. However, the link between MDSCs and glycolysis is unknown in patients with triple-negative breast cancer (TNBC). Here, we detect abundant glycolytic activities in human TNBC. In two TNBC mouse models, 4T1 and Py8119, glycolysis restriction inhibits tumor granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) expression and reduces  ...[more]

Similar Datasets

| S-EPMC8380247 | biostudies-literature
| S-EPMC7481329 | biostudies-literature
| S-EPMC10787506 | biostudies-literature
| S-EPMC4775355 | biostudies-literature
| S-EPMC6205409 | biostudies-literature
| S-EPMC5924419 | biostudies-literature
| S-EPMC8096791 | biostudies-literature
| S-EPMC8275624 | biostudies-literature
| S-EPMC6193703 | biostudies-literature
| S-EPMC8529494 | biostudies-literature