Bone marrow neutrophils regulate multiple myeloma by releasing DNA
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE69834 | GEO | 2018/08/31
REPOSITORIES: GEO
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Project description:Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) are important regulators of immune responses and promoters of tumor progression in cancer1,2. The heterogeneity of these cells as well as their distinction from neutrophils hampers the progress in understanding of the biology and clinical significance of these cells. PMN-MDSC had a distinct gene signature from neutrophils isolated from the same patients with most prominent changes in genes associated with endoplasmic reticulum (ER) stress response. Surprisingly, low-density lipoprotein (LDL) was one of the most enriched gene regulators and oxidized LDL receptor 1 (OLR1) was one of the most overexpressed genes in PMN-MDSC. Lectin-type oxidized LDL receptor 1 (LOX-1) encoded by OLR1 was expressed in only 0.7% of neutrophils in peripheral blood of healthy donors, whereas 5-15% of neutrophils in cancer patients and 15-50% of neutrophils in tumor tissues were LOX-1+. In contrast to their LOX-1- counterparts, LOX-1+ neutrophils had gene signature, biochemical and functional characteristics of PMN-MDSC. Induction of ER stress in neutrophils from healthy donors up-regulated LOX-1 expression and converted these cells to suppressive PMN-MDSC. Thus, PMN-MDSC have distinct gene signature and LOX-1 can define this population of cells, which may provide new insight to the biology and clinical evaluation of these cells. Examination of LOX1+/LOX1- and PMN/MDSC cells in cancer patient samples
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Project description:Pathologically activated neutrophils (PMN), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumor immunity. The mechanisms responsible for the pathological activation of neutrophils upon infiltration into tumors are not well defined, thus limiting the selective targeting of these cells. Tumor cells and immune cells engage in bi-directional manipulation of their respective metabolism, thereby altering cell function to facilitate tumor progression. Targeting the metabolism of responding immune cells can improve cancer treatment when combined with existing therapeutic strategies. Here, we investigated the role of metabolism in the immunoinhibitory actions of tumor PMN-MDSCs.
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