scholarly journals Modulation of Immunity by Antiangiogenic Molecules in Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Magali Terme ◽  
Orianne Colussi ◽  
Elie Marcheteau ◽  
Corinne Tanchot ◽  
Eric Tartour ◽  
...  
Keyword(s):  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunomodulatory Effects ◽  
New Class ◽  
Immune Parameters ◽  
Therapeutic Drugs ◽  
The Impact ◽  
Immunosuppressive Cytokines ◽  
Potential Biomarkers

In the last decades a new class of therapeutic drugs have been developed that block tumor angiogenesis. These antiangiogenic molecules, which target VEGF or VEGFR, PDGFR, and c-kit, can act not only on endothelial cells but also on immune cells. Some antiangiogenic molecules inhibit the development of immunosuppressive mechanisms developed by the tumors to escape the immune system (such as regulatory T cells, myeloid-derived suppressor cells, and immunosuppressive cytokines). These immunomodulatory effects must be characterized in detail to enable a better prescription of these treatments. In this paper we will focus on the impact of anti-angiogenic drugs on immunosuppression and their potential combination with immunotherapeutic strategies. Interestingly, immune parameters or their modulation during treatment could serve as potential biomarkers of response or resistance to anti-angiogenic therapies.

scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSCs) in the Development and/or Progression of Endometriosis-State of the Art

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 677
Author(s):  
Dorota Suszczyk ◽  
Wiktoria Skiba ◽  
Joanna Jakubowicz-Gil ◽  
Jan Kotarski ◽  
Iwona Wertel
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Chronic Inflammation ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunological Diseases ◽  
Underlying Mechanisms ◽  
And Function ◽  
The Impact

Endometriosis (EMS) is a common gynecological disease characterized by the presence of endometrial tissue outside the uterus. Approximately 10% of women around the world suffer from this disease. Recent studies suggest that endometriosis has potential to transform into endometriosis-associated ovarian cancer (EAOC). Endometriosis is connected with chronic inflammation and changes in the phenotype, activity, and function of immune cells. The underlying mechanisms include quantitative and functional disturbances of neutrophils, monocytes/macrophages (MO/MA), natural killer cells (NK), and T cells. A few reports have shown that immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) may promote the progression of endometriosis. MDSCs are a heterogeneous population of immature myeloid cells (dendritic cells, granulocytes, and MO/MA precursors), which play an important role in the development of immunological diseases such as chronic inflammation and cancer. The presence of MDSCs in pathological conditions correlates with immunosuppression, angiogenesis, or release of growth factors and cytokines, which promote progression of these diseases. In this paper, we review the impact of MDSCs on different populations of immune cells, focusing on their immunosuppressive role in the immune system, which may be related with the pathogenesis and/or progression of endometriosis and its transformation into ovarian cancer.

scholarly journals Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models

2020 ◽  
Author(s):  
S. Mahnaz ◽  
L. Das Roy ◽  
M. Bose ◽  
C. De ◽  
S. Nath ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Microenvironment ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Signaling Pathways ◽  
Suppressor Cells ◽  
Ductal Adenocarcinoma ◽  
Myeloid Derived Suppressor Cells ◽  
Mucin 1 ◽  
Transmembrane Glycoprotein ◽  
The Impact

ABSTRACTMyeloid-derived suppressor cells (MDSCs) are immature myeloid cells that are responsible for immunosuppression in tumor microenvironment. Here we report the impact of mucin 1 (MUC1), a transmembrane glycoprotein, on proliferation and functional activity of MDSCs. To determine the role of MUC1 in MDSC phenotype, we analyzed MDSCs derived from wild type (WT) and MUC1-knockout (MUC1KO) mice bearing pancreatic ductal adenocarcinoma KCKO and breast cancer C57MG xenografts. We observed enhanced tumor growth in MUC1KO mice compared to WT mice in both pancreatic KCKO and breast C57MG cancer models due to increased MDSC population and enrichment of Tregs in tumor microenvironment. Our current study shows that knockdown of MUC1 in MDSCs promotes proliferation and immature suppressive phenotype indicated by increased level of iNOS, ARG1 activity and TGF-β secretion under cancer conditions. Increased activity of MDSCs leads to repression of IL-2 and IFN-ɣ production by T-cells. We were able to find that MDSCs from MUC1KO mice have higher levels of c-Myc and activated pSTAT3 as compared to MUC1 WT mice, that are signaling pathways leading to increased survival, proliferation and prevention of maturation. In summary, MUC1 regulates signaling pathways that maintain immunosuppressive properties of MDSCs. Thus, immunotherapy must target only tumor associated MUC1 on epithelial cells and not MUC1 on hematopoietic cells to avoid expansion and suppressive functions of MDSC.

scholarly journals A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2700
Author(s):  
Francesca Hofer ◽  
Gianna Di Sario ◽  
Chiara Musiu ◽  
Silvia Sartoris ◽  
Francesco De Sanctis ◽  
...  
Keyword(s):  
Metabolic Network ◽  
Cancer Progression ◽  
Immune Cells ◽  
Energy Demand ◽  
Tumour Progression ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Proliferation And Differentiation

Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.

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.

scholarly journals Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Jianmin Peng ◽  
Qinchao Hu ◽  
Xijuan Chen ◽  
Chunyang Wang ◽  
Jiayu Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Suppressor Cells ◽  
Underlying Mechanism ◽  
Clinical Samples ◽  
Acid Uptake ◽  
Myeloid Derived Suppressor Cells ◽  
Increased Risk ◽  
The Impact

AbstractAlthough obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b+Gr1+ myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33+ (a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients.

scholarly journals Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Fengqian Chen ◽  
Jingquan Li ◽  
Hui Wang ◽  
Qian Ba
Keyword(s):  
Dendritic Cells ◽  
Chinese Medicine ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Traditional Chinese Medicine ◽  
Tumor Cells ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Adaptive Immune Cells

As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4+/CD8+ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.

scholarly journals Emerging Roles of Myeloid-Derived Suppressor Cells in Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiqi Wang ◽  
Qian Tan ◽  
Yayi Hou ◽  
Huan Dou
Keyword(s):  
Insulin Resistance ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Heterogeneous Population ◽  
Myeloid Derived Suppressor Cells ◽  
Pathological Characteristics ◽  
Myeloid Derived Suppressor Cell ◽  
Combined Action ◽  
Immature Cells

Diabetes is a syndrome characterized by hyperglycemia with or without insulin resistance. Its etiology is attributed to the combined action of genes, environment and immune cells. Myeloid-derived suppressor cell (MDSC) is a heterogeneous population of immature cells with immunosuppressive ability. In recent years, different studies have debated the quantity, activity changes and roles of MDSC in the diabetic microenvironment. However, the emerging roles of MDSC have not been fully documented with regard to their interactions with diabetes. Here, the manifestations of MDSC and their subsets are reviewed with regard to the incidence of diabetes and diabetic complications. The possible drugs targeting MDSC are discussed with regard to their potential of treating diabetes. We believe that understanding MDSC will offer opportunities to explain pathological characteristics of different diabetes. MDSC also will be used for personalized immunotherapy of diabetes.

scholarly journals Arginine and Arginases Modulate Metabolism, Tumor Microenvironment and Prostate Cancer Progression

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4503
Author(s):  
Andreia Matos ◽  
Marcos Carvalho ◽  
Manuel Bicho ◽  
Ricardo Ribeiro
Keyword(s):  
Prostate Cancer ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Urea Cycle ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Prostate Cancer Progression ◽  
Arginine Metabolism ◽  
Arginine Deprivation ◽  
The Impact

Arginine availability and activation of arginine-related pathways at cancer sites have profound effects on the tumor microenvironment, far beyond their well-known role in the hepatic urea cycle. Arginine metabolism impacts not only malignant cells but also the surrounding immune cells behavior, modulating growth, survival, and immunosurveillance mechanisms, either through an arginase-mediated effect on polyamines and proline synthesis, or by the arginine/nitric oxide pathway in tumor cells, antitumor T-cells, myeloid-derived suppressor cells, and macrophages. This review presents evidence concerning the impact of arginine metabolism and arginase activity in the prostate cancer microenvironment, highlighting the recent advances in immunotherapy, which might be relevant for prostate cancer. Even though further research is required, arginine deprivation may represent a novel antimetabolite strategy for the treatment of arginine-dependent prostate cancer.

scholarly journals Granulocytic Myeloid-Derived Suppressor Cells in Breast Milk (BM-MDSC) Correlate with Gestational Age and Postnatal Age and Are Influenced by Infant’s Sex

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2571
Author(s):  
Natascha Köstlin-Gille ◽  
Lara-Antonia Flaig ◽  
Marco Ginzel ◽  
Jörg Arand ◽  
Christian F. Poets ◽  
...  
Keyword(s):  
Breast Milk ◽  
Preterm Infants ◽  
Gestational Age ◽  
Immune Cells ◽  
Intestinal Flora ◽  
Suppressor Cells ◽  
Mucosal Barrier ◽  
Myeloid Derived Suppressor Cells ◽  
Activation Markers ◽  
Causative Agents

Background: Infections are the main cause of death in preterm infants. Causative agents often descend from the intestinal flora of the infected neonate, indicating insufficient protection by the mucosal barrier. Breast milk (BM) contains different subsets of immune cells. We recently showed that BM contains significant numbers of myeloid-derived suppressor cells (MDSC)—immune cells that actively suppress pro-inflammatory immune responses—and hypothesized that the transfer of BM-MDSC may modulate the mucosal immunity of the newborn. Methods: Percentages of MDSC in the BM from mothers of 86 preterm infants between 23 + 0 and 36 + 6 weeks of gestation during their first five postnatal weeks were analyzed by flow cytometry and correlated with maternal and infant characteristics. Results: Percentages of BM-MDSC positively correlated with gestational age and postnatal age. The expression of activation markers on BM-MDSC did not change with gestational age, but it decreased with postnatal age. Mothers who received antepartum tocolytics had lower percentages of BM-MDSC, and infant’s sex strongly influenced percentages of BM-MDSC. Conclusion: Our results point toward a role of BM-MDSC for immune regulation in the neonatal gut, making them a potential target of immune-based therapies shortly after birth.

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