scholarly journals Comparison of Myeloid Cells in Circulation and in the Tumor Microenvironment of Patients with Colorectal and Breast Cancers

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Salman M. Toor ◽  
Eyad Elkord
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Histological Grade ◽  
Clinical Stage ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Therapeutic Agents ◽  
Breast Cancers ◽  
Immature Myeloid Cells ◽  
Poorly Differentiated

We have previously reported levels of myeloid cells in the periphery and in the tumor microenvironment (TME) of patients with primary breast cancer (PBC) and colorectal cancer (CRC). We found that both PBC and CRC patients have significantly higher levels of granulocytic and immature myeloid cells in the TME. Additionally, we reported an expansion of circulating granulocytic myeloid cells in CRC patients, but not in PBC patients. In this report, we compared levels of myeloid cells between these two common cancers and have added data from more cancer patients. We also investigated associations between clinical stage/histological grade of tumors and levels of myeloid cells in cancer patients. We found that although granulocytic myeloid cells were expanded in the TME of both PBC and CRC patients, the levels of these cells were significantly higher in the TME of CRC patients. Moreover, our results indicate that increased levels of circulating granulocytic myeloid cells are associated with poorly differentiated tumors in CRC patients. Taken together, this work suggests that CRC patients may benefit more from the development of therapeutic agents to promote myeloid cell differentiation or inhibition for the reversal of immune suppression.

scholarly journals Myeloid Cells in Circulation and Tumor Microenvironment of Colorectal Cancer Patients with Early and Advanced Disease Stages

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Salman M. Toor ◽  
Sarah Khalaf ◽  
Khaled Murshed ◽  
Mohamed Abu Nada ◽  
Eyad Elkord
Keyword(s):  
Colorectal Cancer ◽  
Tumor Microenvironment ◽  
Cancer Patients ◽  
Whole Blood ◽  
Advanced Disease ◽  
Current Knowledge ◽  
Prognostic Significance ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Disease Stages

Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of cells that have been implicated in the development of an immunosuppressive environment, which promotes tumorigenesis and tumor progression. Numerous studies have reported expansion of MDSCs in circulation and the tumor microenvironment (TME) of cancer patients. However, due to the heterogenic nature of MDSCs and the different approaches for their identification, their detailed characterization and impact on disease progression in cancer patients are warranted. In this study, we investigated the levels of different myeloid cell subsets and antigen-presenting cells (APCs) using flow cytometry in unfractionated whole blood (WB), peripheral blood mononuclear cells (PBMCs), tumor tissue (TT), and adjacent normal tissue (NT) of colorectal cancer (CRC) patients. We found high levels of granulocytic myeloid cells (GMCs) in whole blood, but their levels were significantly lower in PBMCs. Importantly, we found significantly higher levels of GMCs in the TME compared to NT. In addition, monocytic myeloid cells (MMCs) showed significantly higher levels in PBMCs of CRC patients, compared to healthy donors (HDs). Notably, patients with advanced disease stages showed significantly higher levels of GMCs compared to early stages in whole blood, but PBMCs and tumor-infiltrating myeloid cells did not show any significant differences. Lastly, we found that levels of GMCs decreased, while IMCs increased in the TME with tumor budding. Our results highlight the importance of investigating the levels of different myeloid cell subsets in PBMCs versus whole blood of cancer patients and improve current knowledge on the potential prognostic significance of myeloid cells in CRC patients.

IMMU-14. REVEALING THE MANY MYELOID STATES IN HUMAN BRAIN TUMORS AND WAYS TO PERTURB THEM

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi94-vi95
Author(s):  
Tyler Miller ◽  
Chadi El Farran ◽  
Julia Verga ◽  
Charles Couturier ◽  
Zeyu Chen ◽  
...  
Keyword(s):  
Brain Tumor ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Ex Vivo ◽  
Myeloid Cells ◽  
Human Tumor ◽  
Myeloid Cell ◽  
Low Grade ◽  
Tumor Patients ◽  
The Many

Abstract Recent breakthroughs in immunotherapy have revolutionized treatment for many types of cancer, but unfortunately trials of these therapies have failed to provide meaningful life-prolonging benefit for brain tumor patients, potentially due to abundant immunosuppressive myeloid cells in the tumor. Our ultimate goal is to reprogram immunosuppressive tumor associated myeloid cells to an antitumor state to enable effective immunotherapy. Towards this goal, we have deeply characterized the immune microenvironment of more than 50 primary high and low grade gliomas using high-throughput single-cell RNA-sequencing to reveal recurrent myeloid cell states and immunosuppressive programs across IDH1 wild-type and mutant tumors. We have also established a brain tumor organoid model from primary patient tissue that maintains all of the tumor microenvironment, including myeloid and other immune cells. We utilize the this model to functionally test data-driven reprogramming strategies and understand how they impact the states of tumor and immune cells in the ex vivo human tumor microenvironment.

scholarly journals Interleukin 1α (IL-1α) Promotes Pathogenic Immature Myeloid Cells and IL-1β Favors Protective Mature Myeloid Cells During Acute Lung Infection

2018 ◽  
Vol 217 (9) ◽  
pp. 1481-1490 ◽  
Author(s):  
Sivakumar Periasamy ◽  
Jonathan A Harton
Keyword(s):  
Interleukin 1 ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Interleukin 10 ◽  
Dual Function ◽  
Interleukin 17 ◽  
Colony Stimulating Factor ◽  
Immature Myeloid Cells ◽  
Severe Pathology ◽  
Stimulating Factor

Abstract Bacterial pneumonia is a common risk factor for acute lung injury and sepsis-mediated death, but the mechanisms underlying the overt inflammation and accompanying pathology are unclear. Infiltration of immature myeloid cells and necrotizing inflammation mediate severe pathology and death during pulmonary infection with Francisella tularensis. However, eliciting mature myeloid cells provides protection. Yet, the host factors responsible for this pathologic immature myeloid cell response are unknown. Here, we report that while the influx of both mature and immature myeloid cells is strictly MyD88 dependent, the interleukin 1 (IL-1) receptor mediates an important dual function via its ligands IL-1α and IL-1β. Although IL-1β favors the appearance of bacteria-clearing mature myeloid cells, IL-1α contributes to lung infiltration by ineffective and pathologic immature myeloid cells. Finally, IL-1α and IL-1β are not the sole factors involved, but myeloid cell responses during acute pneumonia were largely unaffected by lung levels of interleukin 10, interleukin 17, CXCL1, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor.

Soluble CD138/Syndecan-1 Increases in the Sera of Patients with Moderately Differentiated Bladder Cancer

2014 ◽  
Vol 94 (4) ◽  
pp. 472-478 ◽  
Author(s):  
Mohammad Nabi Sanaee ◽  
Mahyar Malekzadeh ◽  
Abdolaziz Khezri ◽  
Abbas Ghaderi ◽  
Mehrnoosh Doroudchi
Keyword(s):  
Bladder Cancer ◽  
Cell Surface ◽  
Cancer Patients ◽  
Stromal Cells ◽  
Elisa Assay ◽  
Breast Cancers ◽  
Healthy Individuals ◽  
Poorly Differentiated ◽  
Male Patients ◽  
Muscle Invasive

Background: CD138/Syndecan-1 (Sdc-1) is expressed on the tumor and stromal cells of invasive bladder carcinoma. CD138/Sdc-1 shedding from the cell surface is associated with the invasive phenotype in lung and breast cancers. Patients and Methods: Soluble CD138/Sdc-1 was measured in the sera of 86 bladder cancer patients and 57 healthy individuals by a commercial ELISA assay. Results: Soluble Sdc-1 was increased in the sera of patients with bladder cancer (138.42 ± 81.85 vs. 86.48 ± 82.58 ng/ml, p = 0.0003). Patients aged over 70 years had higher levels of CD138/Sdc-1 in their sera (159.7 ± 15.77 vs. 124.5 ± 9.99 ng/ml, p = 0.025), and soluble Sdc-1 levels were higher in the sera of patients with moderately differentiated tumors compared to poorly differentiated ones (170.47 ± 85.06 vs. 101.79 ± 68.24 ng/ml, p = 0.01). The soluble Sdc-1 level was higher in muscle-invasive (154.45 ± 83.60 vs. 89.9 ± 55.02 ng/ml) but not lymphatic-invasive (106.25 ± 52.10 vs. 123.43 ± 63.76 ng/ml) tumors (p = 0.027 and 0.45, respectively). A non-significant trend of soluble Sdc-1 increase in the sera of male patients compared to female patients was observed (145.38 ± 85.47 vs. 110.20 ± 59.04 ng/ml, p = 0.054). Conclusion: The elevated levels of soluble CD138/Sdc-1 in older bladder cancer patients and those with muscular invasion sheds some light on the mechanisms of the disease invasion.

scholarly journals Instruction of myeloid cells by the tumor microenvironment: Open questions on the dynamics and plasticity of different tumor-associated myeloid cell populations

2012 ◽  
Vol 1 (7) ◽  
pp. 1135-1145 ◽  
Author(s):  
Elio Schouppe ◽  
Patrick De Baetselier ◽  
Jo A. Van Ginderachter ◽  
Adelaida Sarukhan
Keyword(s):  
Tumor Microenvironment ◽  
Myeloid Cells ◽  
Myeloid Cell ◽  
Cell Populations ◽  
Open Questions

scholarly journals Increased Production of Immature Myeloid Cells in Cancer Patients: A Mechanism of Immunosuppression in Cancer

2001 ◽  
Vol 166 (1) ◽  
pp. 678-689 ◽  
Author(s):  
Bond Almand ◽  
Joseph I. Clark ◽  
Ekaterina Nikitina ◽  
James van Beynen ◽  
Nicholas R. English ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Myeloid Cells ◽  
Immature Myeloid Cells

scholarly journals Purification and identification of the STAT5 protease in myeloid cells

2007 ◽  
Vol 404 (1) ◽  
pp. 81-87 ◽  
Author(s):  
Björn Schuster ◽  
Lisa Hendry ◽  
Helen Byers ◽  
Steven F. Lynham ◽  
Malcolm A. Ward ◽  
...  
Keyword(s):  
Serine Protease ◽  
Active Form ◽  
Myeloid Cells ◽  
Specific Inhibitor ◽  
Myeloid Cell ◽  
Full Length ◽  
Cathepsin G ◽  
Transactivation Domain ◽  
Immature Myeloid Cell ◽  
Immature Myeloid Cells

STAT (signal transducer and activator of transcription) proteins are critical regulators of cytokine-induced cell proliferation, differentiation and survival. STAT functional activity can be variably regulated by post-translational modifications, including phosphorylation, acetylation, methylation and sumoylation. Additionally, limited proteolytic digestion of full-length STAT proteins (STATα) generates C-terminally truncated forms (STATγ) in different cell lineages, which have significantly reduced transcriptional activity due to the lack of the transactivation domain. Previously, it has been shown that STAT5γ, generated by an unidentified nuclear serine protease, plays an important role in myeloid cell differentiation and is aberrantly expressed in acute myeloid leukaemia. To better understand this regulatory mechanism for STAT5 function, we have purified the STAT5 protease from the immature myeloid cell line 32D and identified it by MS analysis as the granule-derived serine protease, CatG (cathepsin G). We show that purified CatG can specifically cleave full-length STAT5 to generate STAT5γ, and this activity can be inhibited by AEBSF [4-(2-aminoethyl)benzenesulfonyl fluoride] in an in vitro protease assay. Importantly, preparation of nuclear and cytoplasmic extracts from immature myeloid cell lines, 32D and FDC-P1, in the presence of a specific inhibitor for CatG results in the identification of STAT5α only. These studies indicate that nuclear STAT5γ does not naturally exist in immature myeloid cells and is artificially generated from STAT5α during the preparation of extracts due to the abundance of CatG in these cells. Therefore in contrast with earlier studies, our data suggest that STAT5α, rather than STAT5γ is the active form in immature myeloid cells.

scholarly journals Unfavorable Prognostic Effects of the Stem Cell Pluripotency Factor Sox2 in Feline Invasive Mammary Carcinomas

2021 ◽  
Vol 7 ◽  
Author(s):  
Yohan Truchot ◽  
Elie Dagher ◽  
Jérôme Abadie ◽  
Frédérique Nguyen
Keyword(s):  
Estrogen Receptor Alpha ◽  
Histological Grade ◽  
Clinical Stage ◽  
Growth Factor Receptor ◽  
Normal Mammary Gland ◽  
Breast Cancers ◽  
Cancer Specific Survival ◽  
Ki 67 ◽  
Mammary Carcinomas ◽  
Sox2 Expression

Background: Sex-determining Region Y (SRY)-box transcription factor-2 (Sox2) belongs to the “Yamanaka's factors,” necessary and sufficient to convert somatic cells into pluripotent stem cells. In breast cancers, Sox2 expression has been associated with poor prognosis, and resistance to therapy. The aims of this study were to determine the frequency of Sox2 positivity in feline invasive mammary carcinomas (FMCs), its relationships with other clinical-pathologic variables, and with patient outcomes.Materials and Methods: This study relies on a previously described retrospective cohort of 180 FMCs, diagnosed in female cats treated by mastectomy alone, with 2-year follow-up. Sox2 (clone SP76), Estrogen Receptor alpha (ER), Progesterone Receptor (PR), Ki-67, Human Epidermal growth factor Receptor 2 (HER2), Androgen Receptor (AR), Bcl-2, Forkhead box protein A1 (FOXA1), basal markers and FoxP3-positive regulatory T cells (Tregs) were detected by automated immunohistochemistry. Sox2 expression was quantitated as an index (percentage of neoplastic cells demonstrating a positive nuclear signal). The FMCs were considered Sox2-positive at threshold >42%.Results: Sox2 was not expressed in the normal mammary gland or in mammary hyperplasia without atypia, but was occasionally detected in atypical hyperplasia. In FMCs, the mean Sox2 index was 38 ± 30%, and 79/180 FMCs (44%) were Sox2-positive. Sox2 expression was associated with older age at diagnosis, lymphovascular invasion, high Ki-67 proliferation indexes, low PR and FOXA1 expression, and increased numbers of tumor-associated Tregs, but was not significantly associated with the clinical stage, histological types, and histological grade. By multivariate survival analysis, Sox2 was associated with poor cancer-specific survival (Hazard Ratio = 1.48, 95% confidence interval 1.04–2.11, p = 0.0292), independently of the pathologic tumor size, pathologic nodal stage, distant metastasis, and AR expression. A rare subgroup of FMCs characterized by an AR+Sox2–phenotype (19/180 cases, 11%) was associated with very favorable outcomes.Conclusion: Sox2 expression was associated with poor cancer-specific survival of female cats with invasive mammary carcinomas, as previously reported in human breast cancer, but was more commonly expressed in cats than reported in breast cancers. Sox2 showed complementarity with AR in FMC prognostication.

scholarly journals Immature myeloid cells in the tumor microenvironment: Implications for immunotherapy

2018 ◽  
Vol 189 ◽  
pp. 34-42 ◽  
Author(s):  
Neha Kamran ◽  
Mayuri Chandran ◽  
Pedro R Lowenstein ◽  
Maria G Castro
Keyword(s):  
Tumor Microenvironment ◽  
Myeloid Cells ◽  
Immature Myeloid Cells

scholarly journals Myeloid Cells in the Tumor Microenvironment: Modulation of Tumor Angiogenesis and Tumor Inflammation

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Michael C. Schmid ◽  
Judith A. Varner
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Angiogenesis ◽  
Malignant Tumors ◽  
Critical Role ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Myeloid Cell ◽  
Promote Tumor Growth ◽  
Bone Marrow Derived Cells

Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. Furthermore, we describe a subset of myeloid cells with immunosuppressive activity (known as myeloid-derived suppressor cells). Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy.

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