Review

Authors: Claire E Olingy, Huy Q Dinh, Catherine C Hedrick...

Monocytes are innate immune cells of the mononuclear phagocyte system that have emerged as important regulators of cancer development and progression. Our understanding of monocytes has advanced from viewing these cells as a homogenous population to a heterogeneous system of cells that display diverse responses to different stimuli. During cancer, different monocyte subsets perform functions that contribute to both pro- and antitumoral immunity, including phagocytosis, secretion of tumoricidal mediators, promotion of angiogenesis, remodeling of the extracellular matrix, recruitment of lymphocytes, and differentiation into tumor-associated macrophages and dendritic cells. The ability of cancer to evade immune recognition and clearance requires protumoral signals to outweigh ongoing attempts by the host immune system to prevent tumor growth. This review discusses current understanding of monocyte heterogeneity during homeostasis, highlights monocyte functions in cancer progression, and describes monocyte-targeted therapeutic strategies for cancer treatment.

Topics: Animals; Biomarkers; Cell Movement; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunophenotyping; Monocytes; Neoplasms; Tumor Microenvironment

PubMed: 30776148
DOI: 10.1002/JLB.4RI0818-311R

Review

Authors: Alice Coillard, Elodie Segura

Circulating monocytes can infiltrate mucosal or inflamed tissues where they differentiate into either macrophages or dendritic cells. This paradigm is supported by numerous studies conducted in mice and in different settings for human cells. Determining whether it holds true in humans is essential for the successful design of monocyte-targeting therapies. Despite limitations inherent to working with human samples, there is accumulating evidence of the existence of generated monocyte-derived cells in humans. Here, we review recent studies showing the recruitment of human monocytes into tissues and their differentiation into macrophages or dendritic cells, in normal or pathological settings. We examine the methods available in human studies to demonstrate the monocytic origin of infiltrating cells. Finally, we review the functions of human monocyte-derived cells and how they might contribute to pathogeny.

Topics: Animals; Dendritic Cells; Humans; Macrophages; Monocytes; Myelopoiesis

PubMed: 31456804
DOI: 10.3389/fimmu.2019.01907

Review

Authors: Agnieszka Ożańska, Donata Szymczak, Justyna Rybka...

Monocytes are important cells of the innate system. They are a heterogeneous type of cells consisting of phenotypically and functionally distinct subpopulations, which play a specific role in the control, development and escalation of the immunological processes. Based on the expression of superficial CD14 and CD16 in flow cytometry, they can be divided into three subsets: classical, intermediate and non-classical. Variation in the levels of human monocyte subsets in the blood can be observed in patients in numerous pathological states, such as infections, cardiovascular and inflammatory diseases, cancer and autoimmune diseases. The aim of this review is to summarize current knowledge of human monocyte subsets and their significance in homeostasis and in pathological conditions.

Topics: Colony-Stimulating Factors; Humans; Immunity, Innate; Macrophages; Monocytes; Receptors, Cell Surface

PubMed: 32243617
DOI: 10.1111/sji.12883

Authors: Thaize Quiroga Chometon, Mariana da Silva Siqueira, Julie Carmo Sant Anna...

The monocyte-derived dendritic cells (moDCs) are a subset of dendritic cells widely used in immunological studies as a convenient and easy approach after isolation of mononuclear cells directly from peripheral blood mononuclear cells (PBMC). Both the purification and cell culture of monocytes impact on the differentiation of monocytes into moDCs. The methodology to isolate and differentiate monocytes into moDCs is still controversial. We aimed to compare three different protocols for monocyte isolation from PBMC: 1) Cold-aggregation; 2) Percoll gradient; and 3) Magnetic beads cell-enrichment. Additionally we also compared four different monocyte differentiation and culture techniques: 1) Cell culture media; 2) Serum sources; 3) required GM-CSF and IL-4 concentrations; 4) Cell culture systems. We used flow cytometry analysis of light scattering and/or expression of pan surface markers, such as CD3, CD14 and CD209 to determine isolation/differentiation degree. Purified PBMC followed by two steps of cold aggregation, yielded cell viability around 95% with poor monocyte enrichment (monocytes increase vs. lymphocytes reduction was not statistically significant, p>0.05). Conversely, monocyte isolation from PBMC with discontinuous Percoll gradient generated around 50% cell viability. Albeit, we observed a significant reduction (p≤0.05) of lymphocytes contaminants. The magnetic beads cell-enrichment yield cell viability higher than 95%, as high as a significant lymphocyte depletion (p≤0.005) when compared to all other techniques employed. The moDCs showed better differentiation based on increased CD209 expression, but lower CD14 levels, when cells were cultured in RPMI medium plus 500IU/mL of both GM-CSF and IL-4 in a semi-adherent fashion. Serum sources showed no influence on the culture performance. In conclusion, the magnetic beads cell-enrichment showed superior cell viability, indicating that this approach is a better choice to isolate monocytes, and moDCs cultured afterwards in appropriate medium, serum, cytokines and culture system might influence the monocytes differentiation into moDC.

Topics: Antigens, CD; Cell Differentiation; Cell Separation; Cell Survival; Cells, Cultured; Dendritic Cells; Flow Cytometry; Fluorescence; Humans; Monocytes; Scattering, Radiation

PubMed: 32271804
DOI: 10.1371/journal.pone.0231132

Authors: Marc Daigneault, Julie A Preston, Helen M Marriott...

Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD(3)) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD(3) and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells.

Topics: Biomarkers; Blotting, Western; Cell Differentiation; Cell Line; Cytokines; Humans; Lysosomes; Macrophages; Microscopy, Confocal; Mitochondria; Monocytes; Nitric Oxide; Phagocytosis; Tetradecanoylphorbol Acetate

PubMed: 20084270
DOI: 10.1371/journal.pone.0008668

Authors: Claude Lambert, Frank W M B Preijers, Gulderen Yanikkaya Demirel...

In April 2013, a symposium was organized to highlight different aspects of differentiation and activation of the monocyte-macrophage lineage as analyzed on the flow cytometer. Characterization of this lineage requires knowledge of the maturation process from their progenitors that are present in bone marrow up to the mature monocytic cells in peripheral blood, because each monocytic lineage cell with an aberrant phenotype refers to the corresponding maturation stage. A standardized quantitative analysis will facilitate the monitoring of the pathological processes and the clinical features, such as the outcome of treatment. However, changes in marker expression by variation in intensity, asynchronism, and lineage infidelity must be considered. The dynamics of normal marker expressions in early differentiation stages, e.g. molecules like HLA II, CD64 or CD14, give rise to a hypothesis on their possible role in monocyte ontogeny. Besides their usual role in tissue homeostasis, mature macrophages may also play a similar role in hematopoiesis. This meeting highlighted the large potential of flow cytometric tools available for monitoring of all these aspects in the monocytic and macrophage cell lineage. © 2015 International Clinical Cytometry Society.

Topics: Cell Differentiation; Cell Lineage; Flow Cytometry; Humans; Macrophages; Monocytes

PubMed: 26332381
DOI: 10.1002/cyto.b.21280

Review

Authors: Amit A Patel, Simon Yona

Blood monocytes develop in the bone marrow before being released into the peripheral circulation. The circulating monocyte pool is composed of multiple subsets, each with specialized functions. These cells are recruited to repopulate resident monocyte-derived cells in the periphery and also to sites of injury. Several extrinsic factors influence the function and quantity of monocytes in the blood. Here, we outline the impact of sex, ethnicity, age, sleep, diet, and exercise on monocyte subsets and their function, highlighting that steady state is not a single physiological condition. A clearer understanding of the relationship between these factors and the immune system may allow for improved therapeutic strategies.

Topics: Aging; Animals; Environment; Ethnicity; Exercise; Homeostasis; Humans; Inheritance Patterns; Leukopoiesis; Life Style; Monocytes; Sex Characteristics; Sleep

PubMed: 31787976
DOI: 10.3389/fimmu.2019.02581

Review

Authors: Stefania Canè, Stefano Ugel, Rosalinda Trovato...

Cancer immunotherapy relies on either restoring or activating the function of adaptive immune cells, mainly CD8 T lymphocytes. Despite impressive clinical success, cancer immunotherapy remains ineffective in many patients due to the establishment of tumor resistance, largely dependent on the nature of tumor microenvironment. There are several cellular and molecular mechanisms at play, and the goal is to identify those that are clinically significant. Among the hematopoietic-derived cells, monocytes are endowed with high plasticity, responsible for their pro- and anti-tumoral function. Indeed, monocytes are involved in several cancer-associated processes such as immune-tolerance, metastatic spread, neoangiogenesis, and chemotherapy resistance; on the other hand, by presenting cancer-associated antigens, they can also promote and sustain anti-tumoral T cell response. Recently, by high throughput technologies, new findings have revealed previously underappreciated, profound transcriptional, epigenetic, and metabolic differences among monocyte subsets, which complement and expand our knowledge on the monocyte ontogeny, recruitment during steady state, and emergency hematopoiesis, as seen in cancer. The subdivision into discrete monocytes subsets, both in mice and humans, appears an oversimplification, whereas continuum subsets development is best for depicting the real condition. In this review, we examine the evidences sustaining the existence of a monocyte heterogeneity along with functional activities, at the primary tumor and at the metastatic niche. In particular, we describe how tumor-derived soluble factors and cell-cell contact reprogram monocyte function. Finally, we point out the role of monocytes in preparing and shaping the metastatic niche and describe relevant targetable molecules altering monocyte activities. We think that exploiting monocyte complexity can help identifying key pathways important for the treatment of cancer and several conditions where these cells are involved.

Topics: Animals; CCAAT-Enhancer-Binding Protein-alpha; Cell Plasticity; Humans; Immunotherapy; Monocytes; Myeloid-Derived Suppressor Cells; Neoplasms

PubMed: 31447834
DOI: 10.3389/fimmu.2019.01786

Review

Authors: Mohammed Shamim Rahman, Andrew J Murphy, Kevin J Woollard...

Monocytes are heterogeneous effector cells involved in the maintenance and restoration of tissue integrity. Monocytes and macrophages are involved in cardiovascular disease progression, and are associated with the development of unstable atherosclerotic plaques. Hyperlipidaemia can accelerate cardiovascular disease progression. However, monocyte responses to hyperlipidaemia are poorly understood. In the past decade, accumulating data describe the relationship between the dynamic blood lipid environment and the heterogeneous circulating monocyte pool, which might have profound consequences for cardiovascular disease. In this Review, we explore the updated view of monocytes in cardiovascular disease and their relationship with macrophages in promoting the homeostatic and inflammatory responses related to atherosclerosis. We describe the different definitions of dyslipidaemia, highlight current theories on the ontogeny of monocyte heterogeneity, discuss how dyslipidaemia might alter monocyte production, and explore the mechanistic interface linking dyslipidaemia with monocyte effector functions, such as migration and the inflammatory response. Finally, we discuss the role of dietary and endogenous lipid species in mediating dyslipidaemic responses, and the role of these lipids in promoting the risk of cardiovascular disease through modulation of monocyte behaviour.

Topics: Cardiovascular Diseases; Dietary Fats; Dyslipidemias; Humans; Monocytes; Plaque, Atherosclerotic

PubMed: 28300081
DOI: 10.1038/nrcardio.2017.34

Review

Authors: Mingxia Zhao, Houzhen Tuo, Shuhui Wang...

The brain is the most important and complex organ in most living creatures which serves as the center of the nervous system. The function of human brain includes controlling of the motion of the body and different organs and maintaining basic homeostasis. The disorders of the brain caused by a variety of reasons often severely impact the patients' normal life or lead to death in extreme cases. Monocyte is an important immune cell which is often recruited to the brain in a number of brain disorders. However, the role of monocytes may not be simply described as beneficial or detrimental. It significantly depends on the disease models and the stages of disease progression. In this review, we summarized the current knowledge about the role of monocytes and monocyte-derived macrophages during several common brain disorders. Major focuses include ischemic stroke, Alzheimer's disease, multiple sclerosis, intracerebral hemorrhage, and insomnia. The recruitment, differentiation, and function of monocyte in these diseases are reviewed.

Topics: Animals; Brain Diseases; Cell Differentiation; Humans; Inflammation; Macrophages; Mice; Monocytes

PubMed: 32596397
DOI: 10.1155/2020/9396021