Myeloid-derived suppressor cells (MDSCs) are heterogeneous populations of immature myeloid cells, which expand and differentiate in responses to growth factors, cytokines and chemokines derived from cancer cells and then are released from bone marrow to peripheral tissues including tumor sites. MDSCs play important roles not only in T-cell suppression but also in angiogenesis, lymphangiogenesis and metastasis during tumor progression. The influence of tumor cells on the activation and proliferation of myeloid cells has been extensively studied. However little is known about the metabolic status of MDSCs during tumor progression. We therefore try to elucidate the metabolic changes during differentiation of myeloid cells into MDSCs. We have found that myeloid cells up-regulated their glycolytic pathway and immunosuppressive features when encountering cancer cells in vitro. Results from DNA microarray and real-time PCR also revealed that monocytic and granulocytic MDSCs from primary tumor sites of 4T1 tumor-bearing mice promoted their glycolysis in comparison to their healthy counterparts, monocytes and neutrophils, from bone marrow of healthy mice. We further proved that glycolytic pathway contributed to the survival and immunosuppression of MDSCs in vitro and in vivo using a hexokinase inhibitor, 2-DG, to block glycolysis. We are currently examining the association of metabolites from glycolysis and differentiation of myeloid cells during tumor progression and expect to identify specific metabolite responsible for driving differentiation of MDSCs.
Date:
2016-08
Relation:
European Journal of Immunology. 2016 Aug;46(Suppl. 1):213-214.
