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Project description:The Cxcr2+ subset of the S100A8+ Gastric Granylocytic Myeloid-Derived Suppressor Cell Population Regulates Gastric Pathology
| PRJNA1004661 | ENA
Project description:The aim of the study is to evaluate whether the preoperative level of myeloid-derived suppressor cells is associated with postoperative complications classified by Clavien-Dindo categories. Levels of all MDSC, polymorphonuclear MDSC (PMNMDSC), monocytic MDSC (MMDSC), early-stage MDSC (EMDSC) and monocytic to polymorphonuclear MDSC ratio (M/PMN MDCS) were established and compared in patients with postoperative complications, severe postoperative complications (>= IIIA according to Clavien-Dindo) and severe septic complications.
| 2381881 | ecrin-mdr-crc
Project description:A large body of evidence indicates that chronic inflammation is one of several key risk factors for cancer initiation, progression, and metastasis. However, the underlying mechanisms responsible for the contribution of inflammation and inflammatory mediators to cancer remain elusive. Here, we present genetic evidence that loss of CXCR2 dramatically suppresses chronic colonic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid-derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis-associated cancer. CXCR2 ligands were elevated in inflamed colonic mucosa and tumors and induced MDSC chemotaxis. Adoptive transfer of wild-type MDSCs into Cxcr2(-/-) mice restored AOM/DSS-induced tumor progression. MDSCs accelerated tumor growth by inhibiting CD8(+) T cell cytotoxic activity.
| S-EPMC3928012 | biostudies-literature
Project description:Chronic inflammation is associated with promotion of malignancy and tumor progression. Many tumors enhance the accumulation of myeloid-derived suppressor cells (MDSC), which contribute to tumor progression and growth by suppressing anti-tumor immune responses. Tumor-derived IL-1? secreted into the tumor microenvironment has been shown to induce the accumulation of MDSC possessing an enhanced capacity to suppress T cells. In this study, we found that the enhanced suppressive potential of IL-1?-induced MDSC was due to the activity of a novel subset of MDSC lacking Ly6C expression. This subset was present at low frequency in tumor-bearing mice in the absence of IL-1?-induced inflammation; however, under inflammatory conditions, Ly6C(neg) MDSC were predominant. Ly6C(neg) MDSC impaired NK cell development and functions in vitro and in vivo. These results identify a novel IL-1?-induced subset of MDSC with unique functional properties. Ly6C(neg) MDSC mediating NK cell suppression may thus represent useful targets for therapeutic interventions.
| S-EPMC3373225 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) comprise a hetergenous immune cell population that expands within the inflamed microenvironment of the stomach during pre-cancerous and cancerous lesion development in mouse. This study compares gastric CD11b+Ly6G+ cells vetween Cxcr2flox/flox and S100A8CreCxcr2flox/flox after 6 month H. felis infection.
2023-08-14 | GSE240719 | GEO
Project description:Snail is a major transcriptional factor that induces epithelial-mesenchymal transition (EMT). In this study, we explore the effect of Snail on tumor immunity. Snail knockdown in mouse ovarian cancer cells suppresses tumor growth in immunocompetent mice, associated with an increase of CD8+ tumor-infiltrating lymphocytes and a decrease of myeloid-derived suppressor cells (MDSCs). Snail knockdown reduces the expression of CXCR2 ligands (CXCL1 and CXCL2), chemokines that attract MDSCs to the tumor via CXCR2. Snail upregulates CXCR ligands through NF-kB pathway, and most likely, through direct binding to the promoters. A CXCR2 antagonist suppresses MDSC infiltration and delays tumor growth in Snail-expressing mouse tumors. Ovarian cancer patients show elevated serum CXCL1/2, which correlates with Snail expression, MDSC infiltration, and short overall survival. Thus, Snail induces cancer progression via upregulation of CXCR2 ligands and recruitment of MDSCs. Blocking CXCR2 represents an immunological therapeutic approach to inhibit progression of Snail-high tumors undergoing EMT.
| S-EPMC5923228 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) are CD11b+Gr1+ cells that induce T-cell hyporesponsiveness, thus impairing antitumor immunity. We have previously reported that disruption of Pak2, a member of the p21-activated kinases (Paks), in hematopoietic stem/progenitor cells (HSPCs) induces myeloid lineage skewing and expansion of CD11bhighGr1high cells in mice. In this study, we confirmed that Pak2-KO CD11bhighGr1high cells suppressed T-cell proliferation, consistent with an MDSC phenotype. Loss of Pak2 function in HSPCs led to (1) increased hematopoietic progenitor cell sensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling, (2) increased MDSC proliferation, (3) decreased MDSC sensitivity to both intrinsic and Fas-Fas ligand-mediated apoptosis, and (4) promotion of MDSCs by Pak2-deficient CD4+ T cells that produced more interferon γ, tumor necrosis factor α, and GM-CSF. Pak2 disruption activated STAT5 while downregulating the expression of IRF8, a well-described myeloid transcription factor. Together, our data reveal a previously unrecognized role of Pak2 in regulating MDSC development via both cell-intrinsic and extrinsic mechanisms. Our findings have potential translational implications, as the efficacy of targeting Paks in cancer therapeutics may be undermined by tumor escape from immune control and/or acceleration of tumorigenesis through MDSC expansion.
| S-EPMC5728145 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1(+)CD11b(+)Ly6G(med)Ly6C(med) MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27(+)CD11b(+)NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14(+)HLA-DR(-) and CD14(-) HLA-DR(-) MDSC) in NHL patients and found that higher IL-10-producing CD14(+)HLA-DR(-)MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.
| S-EPMC4404816 | biostudies-other
Project description:Methylprednisolone is an effective drug in the treatment of autoimmune disease, such as multiple sclerosis (MS), due to long-acting anti-inflammatory, antiallergic and immunosuppressant. Previous studies have noted the importance of myeloid-derived suppressor cells (MDSC) in MS progression. However, it is still not known whether methylprednisolone could influence the ratio and function of MDSC during MS treatment. In the current study, we found an increased ratio of MDSC at the onset of EAE in mice model; but methylprednisolone pulse therapy (MPPT) did not alter the percentage and suppressive function of MDSC during disease attenuation. However, the percentage of G-MDSC in PBMC significantly increased in patients with MS. Surprisingly, relapsing MS patients showed a significant increase in both M-MDSC and G-MDSC after MPPT. The disease remission positively correlated expansion of MDSC and expression of arginase-1. Additionally, MPPT reduced the expression of inhibitory glucocorticoid (GCs) receptor β subunit on MDSC while elevating serum levels of immune regulatory S100A8/A9 heterodimer. Thus, MDSC dynamics and function in mouse EAE differ from those in human MS during MPPT. Our study suggested that GCs treatment may help relieve the acute phase of MS by expanding MDSC through up-regulating of GR signalling and S100A8/A9 heterodimers.
| S-EPMC7753844 | biostudies-literature
Project description:Chronic Helicobacter pylori infection triggers neoplastic transformation of the gastric mucosa in a small subset of patients, but the risk factors that induce progression to gastric metaplasia have not been identified. Prior to cancer development, the oxyntic gastric glands atrophy and are replaced by metaplastic cells in response to chronic gastritis. Previously, we identified schlafen 4 (Slfn4) as a GLI1 target gene and myeloid differentiation factor that correlates with spasmolytic polypeptide-expressing metaplasia (SPEM) in mice. Here, we tested the hypothesis that migration of SLFN4-expressing cells from the bone marrow to peripheral organs predicts preneoplastic changes in the gastric microenvironment. Lineage tracing in Helicobacter-infected Slfn4 reporter mice revealed that SLFN4+ cells migrated to the stomach, where they exhibited myeloid-derived suppressor cell (MDSC) markers and acquired the ability to inhibit T cell proliferation. SLFN4+ MDSCs were not observed in infected GLI1-deficient mice. Overexpression of sonic hedgehog ligand (SHH) in infected WT mice accelerated the appearance of SLFN4+ MDSCs in the gastric corpus. Similarly, in the stomachs of H. pylori-infected patients, the human SLFN4 ortholog SLFN12L colocalized to cells that expressed MDSC surface markers CD15+CD33+HLA-DRlo. Together, these results indicate that SLFN4 marks a GLI1-dependent population of MDSCs that predict a shift in the gastric mucosa to a metaplastic phenotype.
| S-EPMC4966326 | biostudies-literature