scholarly journals Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis

2021 ◽  
Vol 8 ◽  
Author(s):  
Panpan Liu ◽  
Cong Peng ◽  
Xiang Chen ◽  
Lisha Wu ◽  
Mingzhu Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Skin Lesions ◽  
Myeloid Derived Suppressor Cells ◽  
M2 Macrophages ◽  
Extracellular Signal Regulated Kinase ◽  
Mhc Ii ◽  
Extracellular Signal ◽  
Proliferation And Differentiation

Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206+ M2 macrophages, and CD11c+MHC-II+ dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation.

scholarly journals Myeloid-Derived Suppressor Cells in Immune Microenvironment Promote Progression of Esophagogastric Junction Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Wang ◽  
Haiyan Sun ◽  
Ningning Zhu ◽  
Xianxian Wu ◽  
Zhilin Sui ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Esophagogastric Junction ◽  
Immune Cell ◽  
Suppressor Cells ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Myeloid Derived Suppressor Cells ◽  
M2 Macrophages ◽  
Esophagogastric Junction Adenocarcinoma

Adenocarcinoma of the esophagogastric junction (AEG) is a fatal disease. Accumulating evidence indicates that, for a comprehensive understanding of AEG, studies should be conducted not only to investigate tumor cells, but also the tumor microenvironment (TME). In this study, we collected AEG patient data from The Cancer Genome Atlas, and used the CIBERSORT algorithm to analyze tumor-infiltrating immune cell profiles. The levels of CD8+ T cells and M0 and M2 macrophages were relatively high in AEG tissues. M2 macrophages were abundant in G3 tumors, and neutrophils were associated with poor prognosis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immunosuppressive cells which share a similar origin to neutrophils and macrophages. We further analyzed the levels of MDSCs in AEG patients and healthy donors (HD) using flow cytometry. MDSC levels were elevated at tumor sites, with polymorphonuclear MDSCs (PMN-MDSCs) being the predominant subtype. Circulating MDSCs partly represented cells at the tumor site. We observed that PMN-MDSC levels at tumor sites were positively correlated with advanced staging, low grade, lymph node metastasis, and HER2− status. Immunohistochemistry and immunofluorescence analyses indicated that activation of the STAT3 and NF-κB pathways in MDSCs may be a potential mechanism for cancer progression. Our studies provided a comprehensive perspective involving tumor-infiltrating immune cells, and detailed insights into the proportion of MDSCs in AEG and their clinical significance. Together, these findings may improve our current understanding of cancer progression involving tumor-infiltrating immune cells in the TME.

Myeloid‐derived suppressor cells can be efficiently generated from human hematopoietic progenitors and peripheral blood monocytes

2017 ◽  
Vol 95 (6) ◽  
pp. 538-548 ◽  
Author(s):  
Sílvia Casacuberta‐Serra ◽  
Marta Parés ◽  
Arantxa Golbano ◽  
Elisabet Coves ◽  
Carmen Espejo ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Blood Monocytes ◽  
Hematopoietic Progenitors ◽  
Peripheral Blood Monocytes

LSC Abstract – Peripheral blood myeloid-derived suppressor cells reflect disease status in IPF

2016 ◽  
Author(s):  
Isis Enlil Fernandez ◽  
Flavia Greiffo ◽  
Marion Frankenberger ◽  
Katharina Heinzelmann ◽  
Claus Neurohr ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Suppressor Cells ◽  
Disease Status ◽  
Myeloid Derived Suppressor Cells

Significance of myeloid-derived suppressor cells in squamous cell carcinoma of the head and neck.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6070-6070
Author(s):  
Grace G Kim ◽  
Adam M Zanation ◽  
Nicholas A Taylor ◽  
Carol G. Shores ◽  
Karen P McKinnon ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Advanced Cancer ◽  
Squamous Cell ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Healthy Donors ◽  
Hpv Status

6070 Background: Patients with advanced stage squamous cell carcinoma of the head and neck (SCCHN) have less than 50% 5-year survival rate Human papillomavirus (HPV)-associated SCCHN in oropharyngeal sites have shown better prognosis. Little is known about the role of myeloid-derived suppressor cells (MDSCs) in immune suppression or tumor progression in the setting of SCCHN. Our objective is to evaluate the clinical significance of MDSCs in subjects with SCCHN, HPV-positivity, and advanced cancer staging. Methods: Thirty-three subjects with SCCHN and 10 healthy donors were enrolled in this prospective cohort study. Fresh blood was collected at the time of surgical resection of SCCHN in a tertiary academic center between August 2011 and January 2013. Peripheral blood mononuclear cells (PBMCs) were obtained using Ficoll Hypaque. MDSCs were immunophenotyped as CD14-CD33+CD11b+by flow cytometry. HPV status was determined by in situ hybridization Frequencies of MDSCs in blood of different cohorts were evaluated. Results: Thirty-three subjects (ages 34-83 years, 25 males) with SCCHN were enrolled. Increased numbers of CD14-CD33+CD11b+ cells of total leukocytes were found in HPV-associated SCCHN (median 26.6%, n=11) compared to HPV-negative SCCHN (16.3%, n=19). Interestingly, 3 subjects who previously had HPV-positive SCCHN but with no evidence of disease had 6.24% (n=3) CD14-CD33+CD11b+cells of leukocytes which was higher than healthy donors (3.55%, n=10). Subjects with advanced cancer stages (III-IV) had higher levels of MDSCs (26%, n=19) compared to those with a lower grade (I-II, 15.5%, n=11) regardless of HPV status. Three subjects were lost to follow up. Of the remaining subjects, the overall median follow time was 3 months and subjects who were found to have recurrence, regional or local metastasis had higher frequencies of MDSCs in the blood (26.35%, n=4) compared to those with no evidence of disease (18.5%, n=26) at the time of surgery. Conclusions: This study suggests there is an accumulation of MDSCs in peripheral blood of patients with SCCHN, particularly in HPV-associated SCCHN. Further, increased levels of MDSCs in the peripheral blood are related to more advance cancer stage and poor clinical outcomes.

Evolution of the myeloid-derived suppressor cells in advanced breast cancer and comparative analysis with a healthy population cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2543-2543
Author(s):  
Natalia Palazón-Carrión ◽  
Carlos Jiménez-Cortegana ◽  
Esther Holgado ◽  
Josefina Cruz Jurado ◽  
Jose Luis Alonso Romero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Complete Response ◽  
Advanced Breast ◽  
Healthy Population ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Subtypes ◽  
Disease Stabilization

2543 Background: High levels of myeloid-derived suppressor cells (MDSCs) seem a negative prognostic factor in advanced breast cancer (ABC) patients (pts). Preclinical studies suggest an immunomodulatory effect of some classical anti-tumor agents through alteration of MDSCs homeostasis. We analyzed the association of MDSCs and clinical evolution of ABC pts, taking into account the systemic treatment (tx) modulation of MDSCs levels in pts from two studies (“A”: GEICAM/2015-04 PANGEA-BREAST, NCT03025880 “Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC”, and “B”: PI-0502-2014 “Peripheral blood analyses of immune response induced by 1st line tx of ABC according to clinical guidelines”). Methods: MDSCs (CD33+ CD11b+) levels were determined by flow-cytometry in peripheral blood samples at three time points (basal, at cycles 3 and 6) from: 39 HER2-negative heavily pretreated pts from study “A”, 43 non-pretreated pts (all subtypes) from study “B” and 20 women from a healthy cohort (HC), with no cancer diagnosis. MDSCs levels from the different cohorts were compared and correlated with pts with Clinical Benefit (CB: partial/complete response + disease stabilization) vs pts with Progressive Disease (PD). Results: Tx response was assessed in 33 pts (85%) from study “A” and 39 pts (91%) from study “B”. CB was observed in 11 pts (28%) from study “A” and in 34 (79%) from study “B” while PD was observed in 22 pts (56%) from study “A” and in 5 (12%) from study “B”. Basal MDSCs levels were significantly higher in ABC pts (studies “A”+”B”) than in HC (15.95 vs 0.81 cells/µl, p = 0.009). At cycle 6, MDSCs were considerably lower in pts with CB vs DP (2.90 vs 13.75 cells/µl, p < 0.001). This decrease was more pronounced in study “B” than in study “A” pts (p < 0.001 vs p = 0.074, respectively), probably due to differences in number of events, tumor subtypes and tx between both studies. Conclusions: Our results suggest that ABC pts show alterations in MDSCs and that their decrease along tx may have a positive predictive value, highlighting the importance that immune-competent status may play in the evolution of ABC. MDSCs may represent a target for therapeutic purposes in ABC.

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