Monocytes and cancer: promising role as a diagnostic marker and application in therapy

Interrelationship between a malignant tumor and the immunity are provided by the involvement of both adaptive and innate immune systems. Monocytes are major participants in nonspecific immune response and mediate their key function through refilling the pool of tumor-associated macrophages, dendritic cells and myeloid suppressor cells. All these populations regulate the relationship of tumor-infiltrating immunocompetent cells with tumor cells and with other components of the microenvironment, as well as tumor cell proliferation, angiogenesis, and dissemination. Monocytes, being direct participants of the chronic persistent inflammation, are involved in the inflammation impact on both tumor origin and progression. The study of the molecular mechanisms of monocyte recruitment and differentiation in malignant neoplasms seems to be a promising direction, both for a diagnostic purpose and as a search for targeting molecules for the control of macrophages and dendritic cells in the tumor microenvironment. In this review, the characteristics of peripheral blood monocytes are given, taking into account the heterogeneity of their population. Tie2+ cells and macrophage-polarized CD163+ and CD204+ -monocytes, as well as cancer-associated macrophage-like cells (CAMLs), are described as contributors to cancer disease progression and outcome. The involvement of monocyte subpopulations in the pathogenesis of oncological diseases of different localizations at the stages of the formation of monocyte precursors in the bone marrow, circulation in peripheral blood and differentiation in tumor tissue is shown.

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MONOCYTES, MACROPHAGES, DENDRITIC AND MYELOID SUPPRESSOR CELLS: GENESIS, CLASSIFICATION, IMMUNOBIOLOGICAL PROPERTIES

Proceedings of the National Academy of Sciences of Belarus Medical series ◽

10.29235/1814-6023-2018-15-3-363-382 ◽

2018 ◽

Vol 15 (3) ◽

pp. 363-382

Author(s):

L. P. Titov

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Immune Responses ◽

Autoimmune Diseases ◽

Suppressor Cells ◽

Mononuclear Phagocyte ◽

Natural Immunity ◽

Myeloid Suppressor Cells ◽

T Cell Immune Responses

The article presents the modern data on the most important component of natural immunity – cells of the mononuclear phagocyte system. The questions of origin, the spectrum of expressed markers of differentiation, the classification of monocytes (classical, intermediate, non-classical), macrophages (pro-inflammatory and anti-inflammatory) and dendritic cells (myeloid, plasmacytoid), their immunobiological functions, their role in humoral and T-cell immune responses, anergy and tolerance are considered. The possibility of obtaining cellular immunobiological products (adjuvant and tolerogenic) for immunotherapy of oncological, infectious and autoimmune diseases on their basis is analyzed.

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The effect of human amniotic epithelial cell on dendritic cell differentiation of peripheral blood monocytes: An experimental study

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i6.7286 ◽

2020 ◽

Author(s):

Bahare Keshavarzi ◽

Meraj Tabatabaei ◽

Amir Hasan Zarnani ◽

Fahime Ramezani Tehrani ◽

Mahmood Bozorgmehr ◽

...

Keyword(s):

Dendritic Cells ◽

Amniotic Membrane ◽

Peripheral Blood ◽

Normal Pregnancy ◽

Interleukin 4 ◽

Control Group ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Dendritic Cell Differentiation ◽

Significant Difference

Background: The amniotic membrane plays an important role in maintaining a healthy pregnancy. The main population cells from amniotic membrane include human amnion epithelial cells (hAECs) which have been shown to possess immunomodulatory properties. Objective: The proximity of hAECs with monocyte leads to the generation of tollerogenic dendritic cells. Materials and Methods: hAECs were obtained from normal pregnancy. Peripheral blood monocytes were isolated by anti-CD14 MACS method. Co-cultures of monocytes and hAECs were established in Transwell chambers supplemented with granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) in the absence and presence of lipopolysaccharide (LPS) to produce immature and mature DCs, respectively. Immunophenotyping of the obtained DCs was done through flow cytometry and the production of cytokines was measured by ELISA. Mixed leukocyte Reaction (MLR) was also performed for the functional assessment of DCs. Results: Immunophenotyping of [hAECs - Immature DC (iDC)] and [hAECs - iDC] + LPS cells revealed that the expression of CD1a, CD80, CD86, CD40, HLA-DR, and CD83 markers showed no significant difference as compared with the control group (iDCs and mDCs alone). In the [hAECs-iDCs] + LPS cells, the percentage of CD14 cells at the ratio of 1:2.5 showed significant differences compared to the control group. The production of IL-10 and IL-12 showed no significant difference in any of the cultures as compared to the control groups. Also, co-cultured DCs did not inhibit proliferation of lymphocyte. Conclusion: Our findings show that factors secreted from cultured hAECs are unable to generate of tollerogenic dendritic cells. To achieve a better understanding of other mechanisms more investigations are needed. Key words: Amniotic membrane, Dendritic cells, Human placenta, Immunomodulation, Monocyte.

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High PD-L1/CD274 Expression of Monocytes and Blood Dendritic Cells Is a Risk Factor in Lung Cancer Patients Undergoing Treatment with PD1 Inhibitor Therapy

Cancers ◽

10.3390/cancers12102966 ◽

2020 ◽

Vol 12 (10) ◽

pp. 2966

Author(s):

Dagmar Riemann ◽

Wolfgang Schütte ◽

Steffi Turzer ◽

Barbara Seliger ◽

Miriam Möller

Keyword(s):

Lung Cancer ◽

Dendritic Cells ◽

Risk Factor ◽

Cancer Patients ◽

Peripheral Blood ◽

Therapy Response ◽

Inhibitor Therapy ◽

Strong Positive Correlation ◽

Blood Monocytes ◽

Lung Cancer Patients

The aim of this study was to investigate the expression of the coinhibitory molecule PD-L1/CD274 in monocytes and dendritic cells (DC) in the blood of lung cancer patients undergoing PD1 inhibitor therapy and to correlate data with patient’s outcome. PD-L1/CD274 expression of monocytes, CD1c+ myeloid DC (mDC) and CD303+ plasmacytoid DC (pDC) was determined by flow cytometry in peripheral blood at immunotherapy onset. The predictive value of the PD-L1/CD274-expression data was determined by patients’ survival analysis. Patients with a high PD-L1/CD274 expression of monocytes and blood DC subpopulations rarely responded to PD1 inhibitor therapy. Low PD-L1/CD274 expression of monocytes and DC correlated with prolonged progression-free survival (PFS) as well as overall survival (OS). The highest PD-L1/CD274 expression was found in CD14+HLA-DR++CD16+ intermediate monocytes. Whereas the PD-L1/CD274 expression of monocytes and DC showed a strong positive correlation, only the PD-L1/CD274 expression of DC inversely correlated with DC amounts and lymphocyte counts in peripheral blood. Our results implicate that a high PD-L1/CD274 expression of blood monocytes and DC subtypes is a risk factor for therapy response and for the survival of lung cancer patients undergoing PD1 inhibitor therapy.

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

Immunology and Cell Biology ◽

10.1038/icb.2017.4 ◽

2017 ◽

Vol 95 (6) ◽

pp. 538-548 ◽

Cited By ~ 18

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

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A subset of myeloid dendritic cells derived from peripheral blood monocytes represented a predominant subset characterized by their potential tumor-inhibiting activity

In Vitro Cellular & Developmental Biology - Animal ◽

10.1007/s11626-009-9187-4 ◽

2009 ◽

Vol 45 (7) ◽

pp. 398-404 ◽

Cited By ~ 4

Author(s):

Min Wang ◽

Jun Shi ◽

Yun Wan ◽

Jing Li ◽

Yinghua Yuan

Keyword(s):

Dendritic Cells ◽

Peripheral Blood ◽

Inhibiting Activity ◽

Blood Monocytes ◽

Myeloid Dendritic Cells ◽

Peripheral Blood Monocytes

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Association of myeloid suppressor cells with resistance to checkpoint blockade immunotherapy in urothelial carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.6_suppl.559 ◽

2020 ◽

Vol 38 (6_suppl) ◽

pp. 559-559

Author(s):

Debasish Sundi ◽

Megan Christina Duggan ◽

Himanshu Savardekar ◽

Hyunwoo Kwon ◽

Steven Sun ◽

...

Keyword(s):

Gene Expression ◽

Bladder Cancer ◽

Gene Expression Profiling ◽

Immune Cells ◽

Peripheral Blood ◽

Expression Profiling ◽

Suppressor Cells ◽

Complete Response ◽

Checkpoint Blockade ◽

Myeloid Suppressor Cells

559 Background: Myeloid immune cells such as myeloid derived suppressor cells (MDSC) and tumor associated macrophages (TAM) have been hypothesized to cause resistance to immune checkpoint blockade (ICB). This is a pressing clinical problem for patients with bladder cancer. Here we determined if we could identify immune cells associated with resistance to ICB in the BBN963 mouse model, and if we could identify therapeutic strategies to target those same suppressor immune cells from patients with bladder cancer. Methods: BBN963 subcutaneous allografts were established in C57BL6/J mice. Response to anti-PD-L1 ICB was classified as partial or complete response according to RECIST criteria. Immune cell subsets with the tumors was evaluated by gene expression profiling and flow cytometry. Peripheral blood from patients with bladder cancer was collected under an IRB-approved protocol. MDSC were purified by flow sorting (CD11b+ CD33+ HLA-DRlow/neg) and screened for viability (Annexin-V staining) after 24 hours of exposure to a panel potential MDSC inhibitors. Results: 16/22 (72%) subjects met criteria for partial or complete response, while 6/22 (28%) were classified as anti-PD-L1 non-responders. Mice in the control group had a 0/10 (0%) response to isotype control (IgG) treatment. Monocytic MDSC (CD11b+ Ly6C+) were much more frequent among the intratumoral CD45+ cells of non-responding subjects as compared to control mice. Nanostring immune panel gene expression profiling revealed that combination treatment of tumor bearing mice with anti-PD-L1 plus ibrutinib (a putative MDSC inhibitor) decreased mRNA biomarkers of tumor-infiltrating macrophages. In vitro screening of patient-derived peripheral blood mononuclear cells showed that an inhibitor of the bromodomain and extraterminal domain (BET) family BRD4 specifically decreased MDSC viability. Conclusions: Monocytic MDSC appear to be associated with resistance to anti-PD-L1 ICB in a new murine model. Analysis of MDSC from patients with bladder cancer suggests that these myeloid suppressor cells can be specifically targeted.

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Impairments of Antigen-Presenting Cells in Pulmonary Tuberculosis

Journal of Immunology Research ◽

10.1155/2015/793292 ◽

2015 ◽

Vol 2015 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Ludmila V. Sakhno ◽

Ekaterina Ya. Shevela ◽

Marina A. Tikhonova ◽

Sergey D. Nikonov ◽

Alexandr A. Ostanin ◽

...

Keyword(s):

Dendritic Cells ◽

Pulmonary Tuberculosis ◽

Peripheral Blood ◽

Antigen Presenting Cells ◽

T Cell Response ◽

Blood Monocytes ◽

Peripheral Blood Monocytes ◽

Gm Csf ◽

Antigen Presenting

The phenotype and functional properties of antigen-presenting cells (APC), that is, circulating monocytes and generatedin vitromacrophages and dendritic cells, were investigated in the patients with pulmonary tuberculosis (TB) differing in lymphocyte reactivity toM. tuberculosisantigens (PPD-reactive versus PPD-anergic patients). We revealed the distinct impairments in patient APC functions. For example, the monocyte dysfunctions were displayed by low CD86 and HLA-DR expression, 2-fold increase in CD14+CD16+expression, the high numbers of IL-10-producing cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The macrophages which werein vitrogenerated from peripheral blood monocytes under GM-CSF were characterized by Th1/Th2-balance shifting (downproduction of IFN-γcoupled with upproduction of IL-10) and by reducing of allostimulatory activity in mixed lymphocyte culture. The dendritic cells (generatedin vitrofrom peripheral blood monocytes upon GM-CSF + IFN-α) were characterized by impaired maturation/activation, a lower level of IFN-γproduction in conjunction with an enhanced capacity to produce IL-10 and IL-6, and a profound reduction of allostimulatory activity. The APC dysfunctions were found to be most prominent in PPD-anergic patients. The possible role of APC impairments in reducing the antigen-specific T-cell response toM. tuberculosiswas discussed.

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