جستجوی مقالات مرتبط با کلیدواژه « myeloid derived suppressor cells » در نشریات گروه « پزشکی »

The cytokine storm and lymphopenia are reported in coronavirus disease 2019 (COVID-19). Myeloid-derived suppressive cells (MDSCs) exist in two different forms, granulocyte (G-MDSCs) and monocytic (M-MDSCs), that both suppress T-cell function. In COVID-19, the role of chemokines such as interleukin (IL)-8 in recruiting MDSCs is unclear. A recent report has correlated IL-8 and MDSCs with poor clinical outcomes in melanoma patients. In the current study, we evaluated the frequency of MDSCs and their correlation with serum IL-8 levels in severe COVID-19 patients from Iran. Thirty-seven severe patients (8 on ventilation, 29 without ventilation), thirteen moderate COVID-19 patients, and eight healthy subjects participated in this study between 10th April 2020 and 9th March 2021. Clinical and biochemical features, serum, and whole blood were obtained. CD14, CD15, CD11b, and HLA-DR expression on MDSCs was measured by flow cytometry. COVID-19 patients compared to healthy subjects had a greater frequency of M-MDSCs (12.7±13.3% vs 0.19±0.20%,), G-MDSCs (15.8±12.6% vs 0.35±0.40%,) and total-MDSCs (27.5±17.3% vs 0.55±0.41%,). M-MDSC (16.8±15.8% vs 5.4±4.8%,) and total-MDSC (33.3±18.5% vs 17.3±13.3%) frequency was higher in non- ventilated compared to moderate COVID-19 subjects. Serum IL-8 levels were higher in patients with COVID-19 than in normal healthy subjects (6.4±7.8 vs. 0.10±00 pg/mL). Ventilated patients (15.7±6.7 pg/mL), non-ventilated patients (5.7±2.7 pg/mL) and moderate patients (2.8±3.0 pg/mL) had significantly different levels of IL-8.  A negative correlation was found between the frequency of G-MDSCs and the international normalized ratio (INR) test (r=-0.39), and between the frequency of total-MDSCs and oxygen saturation (%) (r=-0.39). COVID-19 patients with severe non-ventilated disease had the highest levels of M-MDSCs. In addition to systemic MDSCs, lung, serum IL-8, and other inflammatory biomarkers should be measured.

This study is designed to present an agent-based model (ABM) to simulate the interactions between tumor cells and the immune system in the melanoma model. The Myeloid-derived Suppressor Cells (MDSCs) and dendritic cells (DCs) are considered in this model as immunosuppressive and antigen-presenting agents respectively. The animal experiment was performed on 68 B16F10 melanoma tumor-bearing C57BL/6 female mice to collect dynamic data for ABM implementation and validation. Animals were divided into 4 groups; group 1 was control (no treatment) while groups 2 and 3 were treated with DC vaccine and low-dose 5- fluorouracil (5-FU) respectively and group 4 was treated with both DC Vaccine and low-dose of 5-FU. The tumor growth rate, number of MDSC, and presence of CD8+/CD107a+ T cells in the tumor microenvironment were evaluated in each group. Firstly, the tumor cells, the effector immune cells, DCs, and the MDSCs have been considered as the agents of the ABM model and their interaction methods have been extracted from the literature and implemented in the model. Then, the model parameters were estimated by the dynamic data collected from animal experiments.  To validate the ABM model, the simulation results were compared with the real data. The results show that the dynamics of the model agents can mimic the relations among considered immune system components to an emergent outcome compatible with real data. The simplicity of the proposed model can help to understand the results of the combinational therapy and make this model a useful tool for studying different scenarios and assessing the combinational results. Determining the role of each component helps to find critical times during tumor progression and change the tumor and immune system balance in favor of the immune system.

Myeloid-derived suppressor cells (MDSC) are categorized as granulocytic (G-MDSCs) and monocytic (M-MDSCs) and their expansion play a role in cancer progression. Recruitment to the cancer site depends upon the presence of a chemoattractant. We aimed to investigate the presence of MDSC subtypes and of interleukin-8 (CXCL-8) in the peripheral blood in lung cancer subtypes including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients.
Peripheral blood samples of 26 NSCLC patients, 18 SCLC patients, and 8 healthy control donors (HDs) were harvested and the surface expression of CD14, CD15, CD11b, and HLA-DR on MDSCs was measured using flow cytometry. The level of serum CXCL8 was measured by the ELISA method.
The frequency of circulating M-MDSCs was significantly higher in patients with NSCLC than in SCLC and HDs. In contrast, there was no statistical difference concerning the frequency of circulating G-MDSCs between the three groups. The concentration of CXCL-8 was significantly higher in the NSCLC and SCLC patients than in HD control with no significant difference between NSCLC and SCLC groups. There was no correlation between serum CXCL8 and G-MDSC levels.
Our data confirm a higher frequency of circulating M-MDSCs, but not G-MDSCs, in the blood of those suffering from NSCLC but not for SCLC cases. Measuring MDSC subtypes and serum chemotactic factors may have implications for the differential diagnosis of NSCLC.

Melanoma progression and metastasis is suggested to be mediated by increased accumulation of myeloid derived suppressor cells. Various chemotherapeutic drugs such as 5-Fluorouracil in single low concentration have the capacity, at least in part, to reverse tumor progression by reducing myeloid derived suppressor cells-mediated immunosuppression. To assess whether multiple low doses of 5-fluorouracil could repress myeloid derived suppressor cells in low frequency and, in turn, could enhance anti-tumor responses and promote a more prolonged survival in a murine melanoma model. Fifty milligram per kilogram body weight dose of 5-Flourouracil was administered intraperitoneally 4 times with 3-day intervals to C57BL/6 mice after B16 melanoma tumor models were established. The frequency and suppressive functions of myeloid derived suppressor cells and induction of anti-tumor CD8+ T cells as well as tumor growth and survival were evaluated in drug treated and untreated mice. Our results demonstrated that this therapeutic strategy increases the overall mice survival (p≤0.01) and induces melanoma-specific CD8+T cell immunity (p≤0.01) by reducing the frequency of myeloid derived suppressor cells (p≤0.01) as well as their immune suppressive functions (p≤0.05). Altogether, our data suggest that 5-fluorouracil in multiple low regimens might be used to overcome tumor immunosuppression and improve the efficacy and outcome of anti-tumor immune responses in a mouse model.