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Cells
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Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions
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Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 39669

Special Issue Editors

Dr. Justin Lathia

E-Mail Website
Guest Editor
Cleveland Clinic Lerner Research Institute/Case Comprehensive Cancer Center, Cleveland, OH, USA
Interests: glioblastoma; cancer stem cells; myeloid-derived suppressor cells; sex differences; cell communication; immunotherapy
Dr. Defne Bayik

E-Mail Website
Guest Editor
Cleveland Clinic Lerner Research Institute/Case Comprehensive Cancer Center, Cleveland, OH, USA
Interests: myeloid-derived suppressor cells; macrophages; sex differences; immunotherapy; anti-tumor immunity; tumor microenvironment

Special Issue Information

Dear Colleagues,

As you are aware, immunosuppressive myeloid cells, including macrophages, myeloid-derived suppressor cells (MDSCs) and neutrophils, are dysregulated in a wide-spectrum of pathophysiological conditions ranging from cancer to autoimmune diseases to infection. In addition to serving as biomarkers, these cells play a central role in the manifestation and progression of disease states by altering immune response and supporting the disease microenvironment. Mechanisms leading to accumulation of immunosuppressive myeloid cells and their downstream impact remain areas of intense research interest and are promising fields for therapeutic development.

This Special Issue seeks original research papers and reviews from a broad range of topics related to the tumor-promoting role of myeloid cells, their function in autoimmune diseases/inflammatory conditions, changes in the myeloid cells in the context of infection/metabolic diseases, their potential as disease biomarkers, heterogeneity in immunosuppressive mechanisms and altered signaling pathways leading to myeloid cell dysfunction.

We look forward to your contribution.

Dr. Justin Lathia
Dr. Defne Bayik
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • myeloid-derived suppressor cells
  • macrophages
  • granulocytes
  • cancer
  • malignancy
  • inflammation
  • autoimmune diseases
  • infection

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Published Papers (6 papers)

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Review

21 pages, 1572 KiB  
Review
Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy
by Mithunah Krishnamoorthy, Lara Gerhardt and Saman Maleki Vareki
Cells 2021, 10(5), 1170; https://doi.org/10.3390/cells10051170 - 11 May 2021
Cited by 46 | Viewed by 6172
Abstract
The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects [...] Read more.
The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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14 pages, 854 KiB  
Review
Myeloid-Derived Suppressor Cells as Therapeutic Targets in Uterine Cervical and Endometrial Cancers
by Seiji Mabuchi and Tomoyuki Sasano
Cells 2021, 10(5), 1073; https://doi.org/10.3390/cells10051073 - 30 Apr 2021
Cited by 10 | Viewed by 3441
Abstract
Uterine cervical and endometrial cancers are the two most common gynecological malignancies. As demonstrated in other types of solid malignancies, an increased number of circulating or tumor-infiltrating myeloid-derived suppressor cells (MDSCs) have also been observed in uterine cervical and endometrial cancers, and increased [...] Read more.
Uterine cervical and endometrial cancers are the two most common gynecological malignancies. As demonstrated in other types of solid malignancies, an increased number of circulating or tumor-infiltrating myeloid-derived suppressor cells (MDSCs) have also been observed in uterine cervical and endometrial cancers, and increased MDSCs are associated with an advanced stage, a short survival, or a poor response to chemotherapy or radiotherapy. In murine models of uterine cervical and endometrial cancers, MDSCs have been shown to play important roles in the progression of cancer. In this review, we have introduced the definition of MDSCs and their functions, discussed the roles of MDSCs in uterine cervical and endometrial cancer progression, and reviewed treatment strategies targeting MDSCs, which may exhibit growth-inhibitory effects and enhance the efficacy of existing anticancer treatments. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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16 pages, 1476 KiB  
Review
Myelopoiesis during Solid Cancers and Strategies for Immunotherapy
by Tyler J. Wildes, Bayli DiVita Dean and Catherine T. Flores
Cells 2021, 10(5), 968; https://doi.org/10.3390/cells10050968 - 21 Apr 2021
Cited by 7 | Viewed by 8476
Abstract
Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity [...] Read more.
Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity has proven more difficult. The myeloid compartment, including macrophages, neutrophils, and dendritic cells, has a significant impact on the persistence or elimination of tumors. Myeloid cells, specifically in the tumor microenvironment, have direct contact with tumor tissue and coordinate with tumor-reactive T cells to either stimulate or antagonize cancer immunity. However, the myeloid compartment comprises a broad array of cells in various stages of development. In addition, hematopoietic stem and progenitor cells at various stages of myelopoiesis in distant sites undergo significant modulation by tumors. Understanding how tumors exert their influence on myeloid progenitors is critical to making clinically meaningful improvements in these pathways. Therefore, this review will cover recent developments in our understanding of how solid tumors modulate myelopoiesis to promote the formation of pro-tumor immature myeloid cells. Then, it will cover some of the potential avenues for capitalizing on these mechanisms to generate antitumor immunity. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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21 pages, 2359 KiB  
Review
New Insights into the Multifaceted Role of Myeloid-Derived Suppressor Cells (MDSCs) in High-Grade Gliomas: From Metabolic Reprograming, Immunosuppression, and Therapeutic Resistance to Current Strategies for Targeting MDSCs
by Senthilnath Lakshmanachetty, Joselyn Cruz-Cruz, Eric Hoffmeyer, Allison P. Cole and Siddhartha S. Mitra
Cells 2021, 10(4), 893; https://doi.org/10.3390/cells10040893 - 14 Apr 2021
Cited by 31 | Viewed by 7785
Abstract
Cancer cells “hijack” host immune cells to promote growth, survival, and metastasis. The immune microenvironment of high-grade gliomas (HGG) is a complex and heterogeneous system, consisting of diverse cell types such as microglia, bone marrow-derived macrophages (BMDMs), myeloid-derived suppressor cells (MDSCs), dendritic cells, [...] Read more.
Cancer cells “hijack” host immune cells to promote growth, survival, and metastasis. The immune microenvironment of high-grade gliomas (HGG) is a complex and heterogeneous system, consisting of diverse cell types such as microglia, bone marrow-derived macrophages (BMDMs), myeloid-derived suppressor cells (MDSCs), dendritic cells, natural killer (NK) cells, and T-cells. Of these, MDSCs are one of the major tumor-infiltrating immune cells and are correlated not only with overall worse prognosis but also poor clinical outcomes. Upon entry from the bone marrow into the peripheral blood, spleen, as well as in tumor microenvironment (TME) in HGG patients, MDSCs deploy an array of mechanisms to perform their immune and non-immune suppressive functions. Here, we highlight the origin, function, and characterization of MDSCs and how they are recruited and metabolically reprogrammed in HGG. Furthermore, we discuss the mechanisms by which MDSCs contribute to immunosuppression and resistance to current therapies. Finally, we conclude by summarizing the emerging approaches for targeting MDSCs alone as a monotherapy or in combination with other standard-of-care therapies to improve the current treatment of high-grade glioma patients. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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Graphical abstract

20 pages, 588 KiB  
Review
Myeloid Cells in Glioblastoma Microenvironment
by Alessandra De Leo, Alessio Ugolini and Filippo Veglia
Cells 2021, 10(1), 18; https://doi.org/10.3390/cells10010018 - 24 Dec 2020
Cited by 92 | Viewed by 8850
Abstract
Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells [...] Read more.
Glioblastoma (GBM) is the most aggressive, malignant primary brain tumor in adults. GBM is notoriously resistant to immunotherapy mainly due to its unique immune microenvironment. High dimensional data analysis reveals the extensive heterogeneity of immune components making up the GBM microenvironment. Myeloid cells are the most predominant contributors to the GBM microenvironment; these cells are critical regulators of immune and therapeutic responses to GBM. Here, we will review the most recent advances on the characteristics and functions of different populations of myeloid cells in GBM, including bone marrow-derived macrophages, microglia, myeloid-derived suppressor cells, dendritic cells, and neutrophils. Epigenetic, metabolic, and phenotypic peculiarities of microglia and bone marrow-derived macrophages will also be assessed. The final goal of this review will be to provide new insights into novel therapeutic approaches for specific targeting of myeloid cells to improve the efficacy of current treatments in GBM patients. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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Figure 1

14 pages, 1312 KiB  
Review
TIME Is a Great Healer—Targeting Myeloid Cells in the Tumor Immune Microenvironment to Improve Triple-Negative Breast Cancer Outcomes
by Swarnima Singh, Xiang H. F. Zhang and Jeffrey M. Rosen
Cells 2021, 10(1), 11; https://doi.org/10.3390/cells10010011 - 23 Dec 2020
Cited by 12 | Viewed by 3916
Abstract
The word myeloid is derived from the Greek word muelós which means “marrow”. Therefore, myeloid cells are described as cells that arise in the bone marrow. They can be distinguished from lymphoid cells based on their different differentiation trajectories—Lymphoid cells (B and T [...] Read more.
The word myeloid is derived from the Greek word muelós which means “marrow”. Therefore, myeloid cells are described as cells that arise in the bone marrow. They can be distinguished from lymphoid cells based on their different differentiation trajectories—Lymphoid cells (B and T cells) are usually born in the bone marrow, but they need to migrate to lymphoid organs to mature and differentiate usually in response to antigens produced due to infections and diseases like cancer. On the other hand, myeloid cells do not follow this differentiation trajectory. They arise from the bone marrow, and do not need an encounter with antigens to gain their functionality. Thus, while lymphoid cells are a part of the adaptive immune system, myeloid cells are a part of the innate immune system. Hematopoiesis gives rise to two progenitor cells—the common myeloid progenitor (CMP) and the common lymphoid progenitor (CLP). The CMP can give rise to megakaryocytes, erythrocytes, mast cells and myeloblasts. Myeloblasts in turn lead to the formation of basophils, neutrophils, eosinophils and monocytes that can further differentiate into macrophages. This review will focus on macrophages as well as the phenotypes they acquire with the tumor immune microenvironment (TIME) in triple-negative breast cancer (TNBC). It will address how cancer cells in the tumor microenvironment (TME) recruit macrophages and may switch to recruiting neutrophils upon depletion of these tumor-associated macrophages (TAMs). Finally, it will also shed light on past and current treatment options that specifically target these cells and how those affect patient outcomes in TNBC. Full article
(This article belongs to the Special Issue Immunosuppressive Myeloid Cells in Cancer and Pathophysiological Conditions)
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