Myeloid-Derived Suppressor Cells and Costimulatory Molecules in Children With Allergic Rhinitis

2018 ◽  
Vol 128 (2) ◽  
pp. 128-134 ◽  
Author(s):  
Asmaa M. Zahran ◽  
Khaled Saad ◽  
Khalid I. Elsayh ◽  
Abobakr Abdelmoghny ◽  
Mohamed Diab Aboul-Khair ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Allergic Rhinitis ◽  
T Lymphocytes ◽  
Costimulatory Molecule ◽  
Suppressor Cells ◽  
Costimulatory Molecules ◽  
Healthy Controls ◽  
Myeloid Derived Suppressor Cells

Objectives: The aim of this study is to assess the level of myeloid-derived suppressor cells (MDSCs) and the expression of costimulatory molecules CD80 and CD86 on monocytes and their ligands (CD28) on T-lymphocytes in children with allergic rhinitis (AR). Methods: The study included 60 children with AR and 50 controls. Flow cytometry was performed to analyze MDSCs and the expression of costimulatory molecules CD80 and CD86 on monocytes and their ligands (CD28) on T-lymphocytes. Results: The percentages of total and monocytic MDSCs and the expression of costimulatory molecule CD86 on monocytes were significantly higher in children with AR than in healthy controls. In addition, the expressions of CD28 on CD4+ and CD8+ were significantly elevated in AR patients. Conclusion: The present study demonstrated that the percentages of MDSCs were significantly elevated in AR children. Moreover, the expressions of CD28 on CD4+ and CD8+ were significantly higher in children with AR.

scholarly journals Mass Cytometry Identifies a Novel Signature for Myeloid-Derived Suppressor-Cells in Waldenstrom's Macroglobulinemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3976-3976
Author(s):  
Shahrzad Jalali ◽  
Jose Villasboas ◽  
Jie Shi ◽  
Cole Bothun ◽  
Hyojin Kim ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Clinical Trials ◽  
T Cells ◽  
Research Funding ◽  
Cell Function ◽  
Suppressor Cells ◽  
High Dimensional ◽  
Healthy Controls ◽  
Myeloid Derived Suppressor Cells ◽  
Activated T Cells

Myeloid derived suppressor cells (MDSC) are a heterogeneous population of undifferentiated myeloid cells that are expanded and activated in pathological conditions and have the ability to potently suppress T-cell function and thereby contribute to immunosuppression and tumor progression. While there have been studies showing a role for MDSC in a variety of hematological malignancies, no data is available indicating that MDSCs contribute to the tumor progression in Waldenstrom's Macroglobulinemia (WM), an indolent lymphoma characterized by bone marrow (BM) infiltration of lymphoplasmacytic (LPL) cells and increased secretion of monoclonal IgM. In previous work, we have found increased GM-CSF and reduced arginine and cysteine in the BM microenvironment in WM. We hypothesized that this was due to the presence and activity of MDSCs in WM. BM aspirates from WM patients (n=17) were therefore processed to isolate LPL (CD19+/CD138+) cells from the rest of the BM cells (CD19-/CD138-). Sorted (CD19-/CD138-) cells from BM of patients with WM were studied with flow cytometry. Using a sequential gating strategy (lack of lineage markers, low levels of HLADR, CD33+, CD11b+) we identified a population of MDSCs that were then subdivided using CD14 and CD15 expression into total-, monocytic-, or granulocytic- MDSCs (m-MDSC, g-MDSC). We also analyzed unsorted BM cells using cytometry by time-of-flight (CyTOF) in order to further identify and phenotypically characterize the BM MDSC population in a group of WM patients with smoldering (asymptomatic) disease, symptomatic disease, or in remission post-treatment. BM samples from normal subjects were used as a control. Flow cytometry data showed significant higher numbers of MDSC subsets expressing PD-L1 and Arginase1 in WM patients when compared to the normal samples. BM cells from WM patients (n=18) then were compared to controls (n=11), and the absolute number of the total MDSC (p=0.05), m-MDSC (p=0.002), g-MDSC (p=0.02) was increased in WM specimens. When MDSCs from WM or normal monocytes from healthy controls were co-cultured with activated T-cells, the proliferation of activated T-cells in the presence of MDSCs from WM patients was impaired compared to controls, confirming the suppressive role of MDSCs. We then performed high dimensional analysis of the total BM MDSC cells using t-SNEand identified phenotypically distinct MDSC cell populations in the BM that were differentially present when healthy controls were compared to patients with smoldering WM or those with WM needing treatment. Specifically, WM patients needing treatment had increased numbers of a distinct MDSC population that was highly positive for CD163, and CD138. Moreover, conventional markers denoting m-MDSC and g-MDSC, such as CD14 and CD15, were highly expressed in all populations and their pattern of expression did not specifically define the MDSC subtypes, indicating that high dimensional phenotyping further details the MDSC sub-compartments beyond the conventional categorization of MDSC using conventional cytometry. In summary, we find that MDSCs are increased in the BM of WM patients compared to controls. MDSCs expressing CD163 and CD138 increase when WM patients become symptomatic and require therapy. Furthermore, MDSCs in the BM of WM patients suppress T-cell function and likely contribute to progression of the disease. MDSCs in the BM therefore present a therapeutic target that should be explored in WM patients. Disclosures Ansell: Bristol Myers Squibb: Other: research funding for clinical trials; Merck: Other: research funding for clinical trials; AI Therapeutics: Other: research funding for clinical trials; Affimed: Other: research funding for clinical trials; Takeda: Other: research funding for clinical trials; Pfizer: Other: research funding for clinical trials; Regeneron: Other: research funding for clinical trials; Seattle Genetics: Other: research funding for clinical trials.

scholarly journals The Expansion of Myeloid-Derived Suppressor Cells Is Associated with Joint Inflammation in Rheumatic Patients with Arthritis

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Junqing Zhu ◽  
Shixian Chen ◽  
Lisheng Wu ◽  
Ran Wang ◽  
Songyuan Zheng ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Disease Activity ◽  
Rheumatic Diseases ◽  
Clinical Characteristics ◽  
Suppressor Cells ◽  
Joint Inflammation ◽  
Healthy Controls ◽  
Myeloid Derived Suppressor Cells ◽  
Increased Risk ◽  
Rheumatic Patients

Introduction. We investigated the proportion of myeloid-derived suppressor cells (MDSCs) and their subsets in patients with rheumatic diseases and clarified the association between these cells and the patient clinical data.Methods. Patients with rheumatic diseases and healthy controls were recruited. The clinical characteristics were obtained. The MDSCs and their subsets were marked with fluorescently labelled antibodies and were then analyzed with flow cytometry.Results. The patients included 31 with RA, 21 with AS, 14 with OA, 11 with SLE with arthritis, 13 with SLE without arthritis, 9 with Gout, 10 with HUA, and 25 healthy controls. The proportions of MDSCs, M-MDSCs, and G-MDSCs were higher in patients with RA than in healthy controls (6.56±6.77% versus 1.46±0.96%, 2.52±3.81% versus 0.35±0.35%, and 1.13±1.64% versus 0.18±0.14%; p<0.001). The same increased cells were also found in other patients. The proportions of MDSCs and M-MDSCs were mostly correlated with the patient's joint inflammation indexes and the disease activity. When other cell subsets were adjusted, the increased risk of arthritis was also obtained for M-MDSCs (adjusted OR=5.772; p=0.031).Conclusions. The expansion of MDSCs and their subsets was correlated with the disease activity and joint inflammation in patient with different rheumatic diseases. The proportion of M-MDSCs was associated with the risk of arthritis in those populations.

Increased Blood Monocytic Myeloid Derived Suppressor Cells but Low Regulatory T Lymphocytes in Patients with Mild COVID-19

2021 ◽  
Author(s):  
Carlos Jiménez-Cortegana ◽  
Julia Liró ◽  
Natalia Palazón-Carrión ◽  
Elena Salamanca ◽  
Jesús Sojo-Dorado ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Regulatory T Lymphocytes

Myeloid-Derived Suppressor Cells Increase in Chronic Myeloid Leukemia and Exert Immune Suppressive Activity.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2779-2779
Author(s):  
Cesarina Giallongo ◽  
Nunziatina Parrinello ◽  
Daniele Tibullo ◽  
Piera La Cava ◽  
Alessandra Cupri ◽  
...  
Keyword(s):  
T Cell ◽  
Chronic Myeloid Leukemia ◽  
T Lymphocytes ◽  
Enzymatic Activity ◽  
Myeloid Leukemia ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Arginase 1

Abstract Abstract 2779 Background: Tumor cells are able to develop immune evasion mechanisms which induce a state of immune tolerance and inactivate tumor-specific T cells. In this context, in some solid tumors it has been demonstrated that a subpopulation of myeloid cells, defined as “myeloid-derived suppressor cells” (MDSCs), plays an important role in inducing T cell tolerance by production of arginase that depletes microenvironment of arginine, an essential aminoacid for T cell function. Since chronic myeloid leukemia (CML) patients have high levels of immature myeloid cells it is of interest to investigate if these cells have MDSCs phenotype and activity. Aim: The aim of this study was to analyze MDSCs and investigate their involvement in T-cell anergy of CML patients. Methods: MDSCs were analyzed in peripheral blood (PB) of 13 CML patients (at diagnosis and during therapy) and healthy donors (HD; n=20) by cytofluorimetric analysis (CD14+DR- for monocytic MDSCs and CD11b+CD33+CD14-DR- for granulocytic MDSCs). Arginase 1 expression was assessed in PB of HD and CML patient using real time PCR. Purification of granulocytes, monocytes and lymphocytes from PB was performed by a positive magnetic separation kit (EasySep, STEMCELL Technologies). Arginase activity was measured in granulocyte lysates using a colorimetric test after enzymatic activation and arginine hydrolysis. To evaluate the activation of CD3+ T lymphocytes after incubation with phytoemagglutinin, we analyzed at 24, 48, 72 h the following markers: CD69+, CD71+, DR+. Microvesicles were isolated from CML serum at diagnosis (n=5) by sequential ultracentrifugation. Results: CML patients showed high levels of monocytic and granulocytic MDSCs at diagnosis in comparison to HD (63±8 and 83±12,2% respectively in CML vs 4,9±2,1 and 55,8±5,3% respectively in HD; p<0.001) while after 3–6 months of tyrosine kinase inhibitors (TKIs) therapy MDSC levels returned to normal values. Either in PB and in the purified granulocytes subpopulation, arginase1 expression showed a 30 fold increase in CML at diagnosis (CML vs HD: p<0.01) and decreased after therapy. We also evaluated arginase enzymatic activity in granulocytes and we found it increased in CML patients (n=4) compared to HD (n=5) (p<0.05). CML as well as HD T lymphocytes showed a normal activation in vitro which was significantly lost when they was incubated with CML serum (n=4). In addition, an increase of monocytic MDSCs in vitro was observed after incubation of HD monocytes with CML serum (39±6%; p<0.01) or microvescicles (9,2±1,2%; p<0.05) compared to control serum. Conclusions: Granulocytic and monocytic MDSCs are increased in CML patients at diagnosis and decrease during TKIs treatment. Their levels also correlates with Arginase 1 expression and enzymatic activity in granulocytes. CML serum as well as CML microvesicles increase the percentage of HD monocytic MDSCs. Moreover, CML serum leads to anergy of T lymphocytes, probably by Arginase 1 secretion. Disclosures: Off Label Use: Eltrombopag is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP).

scholarly journals Interferon alpha-induced reduction in the values of myeloid-derived suppressor cells in melanoma patients

2015 ◽  
Vol 72 (4) ◽  
pp. 342-349 ◽  
Author(s):  
Ivan Stanojevic ◽  
Milomir Gacevic ◽  
Milena Jovic ◽  
Zeljko Mijuskovic ◽  
Rados Zecevic ◽  
...  
Keyword(s):  
Interferon Alpha ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Myeloid Derived Suppressor Cells ◽  
Interferon Alpha Therapy ◽  
Significant Difference ◽  
Alpha Effect ◽  
Melanoma Patients ◽  
Alpha Therapy

Background/Aim. Interaction between tumor cells and host?s immunoregulatory cells in creation of microenvironment that supports tumor progression is the focus of numerous investigations in recent years. Myeloid-derived suppressor cells (MDSCs) are heterogeneous population of immature dendritic cells, macrophages and granulocytes. In cancer patients, these cells accumulate in tumor microenvironment, tumor-draining lymph nodes, peripheral blood and the liver and their numbers correlate with the stage of the disease and the metastatic disease. The aim of the study was to investigate the effect of interferon alpha on MDSCs percentage in peripheral blood of melanoma patients. Methods. The interferon treated melanoma patients were given subcutaneously interferon alpha, in optimal dose, for a period of at least 6 months before the analysis. Blood samples were collected from the melanoma patients (n = 91) and the age/sex matched healthy controls (n = 8). The following anti-human monoclonal antibodies were used for immunostaining: anti-CD15-FITC, anti-CD33-PE, anti-CD45-ECD, anti-HLA-DR PE/Cy5, anti-CD14-FITC, anti-CD16-PE and anti-CD11b-PE. Results. Comparison of myeloid-derived suppressor cells values in the stage 2 melanoma patients with and without interferon alpha therapy did not show a significant difference. When we compared the MDSCs values in the patients within stage 3 melanoma, we found a significant difference in granulocytic subset values between the interferon alpha-treated and the untreated group. Comparison of values of all suppressor cells populations between the interferon alpha-treated patients and healthy controls showed a significant increase in suppressor cells percentage in the melanoma patients. The granulocytic and total MDSCs values were significantly lower in the interferon alpha treated melanoma patients with progression in comparison with untreated patients with stable disease. Conclusion. We confirmed that interferon alpha effect in stage 3 melanoma patients was reduction in MDSCs percentage. We also found an unexpected bounce back of these suppressor cells levels, many months after the discontinuation of interferon alpha therapy.

scholarly journals IMPACT OF ENDOSTATIN GENE THERAPY ON MYELOID-DERIVED SUPPRESSOR CELLS FROM A METASTATIC RENAL CELL CARCINOMA

2018 ◽  
Vol 40 (1) ◽  
pp. 24-32
Author(s):  
K CB Chaves ◽  
E M Costa ◽  
L F Teixeira ◽  
M H Bellini
Keyword(s):  
Gene Therapy ◽  
Renal Cell Carcinoma ◽  
Flow Cytometry ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Metastatic Progression

Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b+Gr-1+ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b+Gr-1+ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b+Gr-1+ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b+Gr-1+ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment.

scholarly journals Circulating Myeloid-Derived Suppressor Cells Reflect Mycosis Fungoides/Sezary Syndrome Disease Stage and Response to Treatment

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4127-4127
Author(s):  
Christopher B. Hergott ◽  
Graham Dudley ◽  
David M. Dorfman
Keyword(s):  
Flow Cytometry ◽  
Disease Progression ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Disease Spread ◽  
Sézary Syndrome ◽  
Sezary Syndrome ◽  
Myeloid Derived Suppressor Cells ◽  
Prognostic Information ◽  
Healthy Donors

Abstract Background: Despite mycosis fungoides (MF) and Sezary syndrome (SS) comprising the most common forms of cutaneous T cell lymphoma, the pathophysiology underlying these disorders remains poorly understood. Consequently, current prognostic guidelines based on disease spread exhibit wide variations in clinical outcome within each stage, underscoring an urgent need for novel approaches to MF/SS disease evaluation. A growing body of research suggests that systemic immune dysregulation represents an early, cardinal feature of MF/SS. We hypothesized that tracking this immune dysfunction in conjunction with disease spread may generate important pathophysiologic and prognostic information for patients. We focused on myeloid-derived suppressor cells (MDSCs), a recently discovered population of immunosuppressive innate immune cells related to neutrophils and monocytes, because their expansion in numerous solid tumor settings have correlated reliably with poor patient outcomes. Whether MF/SS augments circulating MDSC abundance remains unexplored, prompting us to evaluate whether this could serve as a marker for disease progression and treatment response. Methods: We used multiparametric flow cytometry to analyze the frequency and immunophenotype of MDSCs from the peripheral blood of 15 healthy donors and 30 patients with MF/SS. Patients at varying stages of MF/SS disease progression and treatment were included in the study. We defined granulocytic MDSCs (G-MDSCs) as cells positive for CD15, CD11b, and the recently discovered surface marker LOX-1, and negative for CD14. Monocytic MDSCs (M-MDSCs) were defined as cells positive for CD14 and CD11b, negative for CD15, and low/negative for HLA-DR. Each patient sample also underwent flow cytometry evaluating for circulating neoplastic T cells. These results were correlated with each participant's other hematologic parameters and clinical information through manual chart review. Results: We found that healthy donors harbored no quantifiable circulating MDSCs of either monocytic or granulocytic lineage, a result in keeping with previous studies. In contrast, MF/SS patients exhibited robust, statistically significant increases in the frequencies of both G-MDSCs and, to a lesser extent, M-MDSCs. G-MDSCs exceeded 20% of all CD15-positive cells in some patients. When patients were stratified by MF/SS clinical stage, those with more advanced disease displayed significantly higher G-MDSC abundance than early-stage patients. G-MDSC frequency was positively correlated with circulating CD4+ CD26- T cell counts often used in evaluating Sezary syndrome (R2 = 0.498; p < 0.0001). However, patients with early, skin-restricted disease also showed statistically significant increases in circulating G-MDSCs compared to healthy controls. This suggested that G-MDSC expansion may serve as a sensitive, blood-based disease marker even in the absence of systemic involvement by neoplasia. Patients who underwent recent treatment exhibited variable G-MDSC counts in the peripheral blood that were lower than in similar untreated patients on average. Serial measurements for two patients enrolled in a clinical trial for dual phosphoinositide 3-kinase and histone deacetylase inhibition revealed that G-MDSC frequencies markedly decreased over the course of treatment, mirroring the decrements of aberrant T cells circulating in the blood. Conclusion: These findings provide clear evidence of G-MDSC expansion in the peripheral blood of MF/SS patients that begins in early/locally restricted disease, grows with disease progression, and responds to systemic therapy. Such immunometric assays may illuminate a novel source of staging and prognostic information and may permit less invasive disease monitoring than current methods require. Disclosures No relevant conflicts of interest to declare.

scholarly journals Circulating Immune Biomarkers in Peripheral Blood Correlate With Clinical Outcomes in Advanced Breast Cancer

2021 ◽  
Author(s):  
Natalia Palazón-Carrión ◽  
Carlos Jiménez-Cortegana ◽  
M. Luisa Sánchez-León ◽  
Fernando Henao-Carrasco ◽  
Esteban Nogales-Fernández ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
T Lymphocytes ◽  
Regulatory T Cells ◽  
Advanced Breast Cancer ◽  
Peripheral Blood ◽  
Clinical Benefit ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immune Biomarkers

Abstract Identification of the different elements intervening at the immunoedition process, in each body compartment, seems key to explain clinical evolution in several tumor types. In this study, a set of immune biomarkers (myeloid derived suppressor cells, regulatory T cells, and OX40+ and PD-1+ T lymphocytes counts) in peripheral blood of patients diagnosed with advanced breast cancer, were analyzed prior to and along the implementation of first line antineoplastic therapy. Subsequently, a formal comparison between groups with clinical benefit versus progression of disease and with a healthy women cohort was executed. Results reflected that patients basally showed higher levels of myeloid derived suppressor cells (35.43, IR=180.73 vs 17.53, IR=16.96 cells/μl; p=0.001) and regulatory T cells (32.05, IR=29.84 vs 22.61, IR=13.57 cells/μl; p=0.001) in comparison with healthy women. Furthermore, after therapy, an increase in the number of activated T lymphocytes (expressing OX40), and a decrease of immune inhibitory cells (MDSCs, and Tregs), and the number of inhibited (or exhausted) T lymphocytes (expressing PD-1), could be ascertained in patients with clinical benefit (p≤0.001). The opposite trend was observed in the case of disease progression. These findings suggest that some critical immune elements can be easily detected and measured in peripheral blood, which open a new opportunity for translational research, as they seem to be clearly correlated with clinical evolution, at least in ABC.

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