Increased Frequency of Myeloid-Derived Suppressor Cells in Myasthenia Gravis After Immunotherapy
Ontology highlight
ABSTRACT:
SUBMITTER: Wang Y
PROVIDER: S-EPMC9278661 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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:Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated autoimmune disease. Little is known about its cellular pathogenesis in dogs. This study provides the first preliminary assessment of the frequency of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the peripheral blood of dogs with seropositive generalized MG. No alteration in frequency of either MDSCs or Tregs in dogs with MG was observed when compared to those in either seronegative dogs with diagnoses other than MG, or healthy dogs. A longitudinal study in three dogs with MG revealed no correlation between the relative numbers of either population and the clinical course of disease. Neither the frequency of MDSCs nor of Tregs showed a correlation with anti-AChR antibody titer in dogs with MG. These findings suggest that aberrations in the frequency of either immunosuppressive population do not occur in MG, but they need to be validated in large-scale prospective studies.
| S-EPMC7780263 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs), which are activated under pathological conditions, are a group of heterogeneous immature myeloid cells. MDSCs have potent capacities to support tumor growth via inhibition of the antitumoral immune response and/or the induction of immunosuppressive cells. In addition, multiple studies have demonstrated that MDSCs provide potential therapeutic targets for the elimination of immunosuppressive functions and the inhibition of tumor growth. The combination of targeting MDSCs and other therapeutic approaches has also demonstrated powerful antitumor effects. In this review, we summarize the characteristics of MDSCs in the tumor microenvironment (TME) and current strategies of cancer treatment by targeting MDSCs.
| S-EPMC7564060 | biostudies-literature
Project description:The clinical responses observed following treatment with immune checkpoint inhibitors (ICIs) support immunotherapy as a potential anticancer treatment. However, a large proportion of patients cannot benefit from it due to resistance or relapse, which is most likely attributable to the multiple immunosuppressive cells in the tumor microenvironment (TME). Myeloid-derived suppressor cells (MDSCs), a heterogeneous array of pathologically activated immature cells, are a chief component of immunosuppressive networks. These cells potently suppress T-cell activity and thus contribute to the immune escape of malignant tumors. New findings indicate that targeting MDSCs might be an alternative and promising target for immunotherapy, reshaping the immunosuppressive microenvironment and enhancing the efficacy of cancer immunotherapy. In this review, we focus primarily on the classification and inhibitory function of MDSCs and the crosstalk between MDSCs and other myeloid cells. We also briefly summarize the latest approaches to therapies targeting MDSCs.
| S-EPMC9513992 | biostudies-literature
Project description:The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies.
| S-EPMC8150533 | biostudies-literature
Project description:BACKGROUND:To investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort. METHODS:Patient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients. RESULTS:14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course. CONCLUSION:A small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.
| S-EPMC7109164 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) are immune cells of the myeloid lineage that progressively accumulate in tumors and play an important role in promoting tumor growth. MDSCs interact with other immune cells present in the tumor microenvironment (TME) and utilize multiple mechanisms to promote immunosuppression. On the other hand, natural killer (NK) cells are cytotoxic cells of the innate immune system and work as one of the first lines of defense against tumors. However, the role of MDSCs in regulating or suppressing NK cells within the TME is poorly understood. This review discusses MDSC-associated immunosuppression, the mechanisms regulating communication between MDSCs and NK cells in the tumor microenvironment, and how MDSC may impact NK-cell-based immunotherapies. We also explore various strategies to increase NK cell cytotoxicity by blocking MDSC-mediated immunosuppression with the goal of enhancing cell based anti-cancer therapeutics.
| S-EPMC9189042 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) are one of the major negative regulators in tumor microenvironment (TME) due to their potent immunosuppressive capacity. MDSCs are the products of myeloid progenitor abnormal differentiation in bone marrow, which inhibits the immune response mediated by T cells, natural killer cells and dendritic cells; promotes the generation of regulatory T cells and tumor-associated macrophages; drives the immune escape; and finally leads to tumor progression and metastasis. In this review, we highlight key features of MDSCs biology in TME that are being explored as potential targets for tumor immunotherapy. We discuss the therapies and approaches that aim to reprogram TME from immunosuppressive to immunostimulatory circumstance, which prevents MDSC immunosuppression activity; promotes MDSC differentiation; and impacts MDSC recruitment and abundance in tumor site. We also summarize current advances in the identification of rational combinatorial strategies to improve clinical efficacy and outcomes of cancer patients, via deeply understanding and pursuing the mechanisms and characterization of MDSCs generation and suppression in TME.
| S-EPMC10063857 | biostudies-literature
Project description:Myeloid-derived suppressor cells (MDSCs) are increased in inflammatory and autoimmune disorders and orchestrate immune cell responses therein. Pulmonary hypertension (PH) is associated with inflammation, autoimmunity, and lung vascular remodeling. Immature myeloid cells are found in the lungs of humans and animals with PH, and we hypothesized that they would be increased in the blood of patients with PH compared with control subjects.Twenty-six children with PH and 10 undergoing cardiac catheterization for arrhythmia ablation were studied. Five milliliters of fresh blood were analyzed using flow cytometry. Results were confirmed using magnetic bead sorting and immunofluorescence, while quantitative polymerase chain reaction and intracellular urea concentration assays were used as measures of MDSC arginase-1 activation.Flow cytometry demonstrated enrichment of circulating MDSCs among patients with PH (n = 26; mean, 0.271 × 10(6) cells/mL ± 0.17; 1.86% of CD45(+) population ± 1.51) compared with control subjects (n = 10; mean, 0.176 × 10(6) cells/mL ± 0.05; 0.57% of CD45(+) population ± 0.29; P < .05). Higher numbers of circulating MDSCs correlated to increasing mean pulmonary artery pressure (r = 0.510, P < .05). Among patients with PH, female patients had a twofold increase in MDSCs compared with male patients. Immunofluorescence analysis confirmed the results of flow cytometry. Quantitative reverse transcription polymerase chain reaction assay results for arginase-1 and measurement of intracellular urea concentration revealed increased activity of MDSCs from patients with PH compared with control subjects.Circulating activated MDSCs are significantly increased in children with PH compared with control subjects. Further investigation of these cells is warranted, and we speculate that they might play significant immunomodulatory roles in the disease pathogenesis of PH.
| S-EPMC3318947 | biostudies-other
Project description:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice. We compared the frequency and function of MDSC subsets in dissociated human spleen from 16 patients with benign pancreatic cysts and 26 patients with a variety of cancers. We found that total MDSCs (Linneg CD11bpos CD33pos HLA-DRneg), granulocytic MDSCs (additional markers CD14neg CD15pos), and monocytic MDSCs (CD14pos CD15neg) were identified in human spleen. The monocytic subset was the most prominent in both spleen and peripheral blood and the granulocytic subset was expanded in the spleen relative to matched peripheral blood samples. Importantly, the frequency of CD15pos MDSCs in the spleen was increased in patients with cancer compared to patients with benign pancreatic cysts and was associated with a significantly increased risk of death and decreased overall survival. Finally, MDSCs isolated from the spleen suppressed T cell responses, demonstrating for the first time the functional capacity of human splenic MDSCs. These data suggest that the human spleen is a potential source of large quantities of cells with immunosuppressive function for future characterization and in-depth studies of human MDSCs.
| S-EPMC5580403 | biostudies-literature