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Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 October 2019) | Viewed by 44437

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Special Issue Editors

Prof. Dr. Ali S. Arbab

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Guest Editor

Tumor Angiogenesis laboratory, Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA
Interests: glioblastoma, tumor microenvironment, neovascularization, anti-angiogenic therapy, vascular mimicry, myeloid derived supressor cells, stem cell tracking, cancer imaging

Prof. Dr. Hasan Korkaya

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Guest Editor

Georgia Cancer Center, Department of Biochemistry and Molecular Biology, Augusta University, Augusta, GA 30912, USA
Interests: breast cancer; metastasis; tumor microenvironment; MDSCs; tumor plasticity; cancer stem cells

Special Issue Information

Dear Colleagues,

Accumulating evidence suggests that tumour-induced immune cells of myeloid origin differentiate into cells that promote tumour growth and invasion in addition to their immunosuppressive role. Although myeloid-derived suppressor cells (MDSC) were initially identified in cancer patients and mouse models due to their potent immune-suppressive activity, they are now being implicated in the promotion of tumour metastasis by participating in the formation of pre-metastatic niches, angiogenesis and invasion. MDSCs are heterogeneous populations of immature myeloid cells that include monocytic (mMDSC) and granulocytic (gMDSC) subsets, both of which have been shown to be immune-suppressive. However, molecular, biochemical and functional characterizations of the MDSCs in preclinical and clinical settings remain to be explored. Furthermore, the fact that MDSCs are major impediments in conventional as well as targeted therapies provided a compelling rationale to develop and design alternative strategies to target MDSCs.

In this Special Issue of IJMS, editors invite authors to submit work which involves the molecular, biochemical and functional characterization of MDSCs in preclinical and clinical settings. In addition, we invite studies that explore the development and design of targeted therapeutics against MDSCs.

Prof. Dr. Ali S. Arbab
Prof. Dr. Hasan Korkaya
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 cells
MDSC subsets
immunesuppression
immune modulator
tumor Microenvironment and MDSC
vasculogenic myeloid cells
MDSC and metastasis
tumor plasticity

Published Papers (6 papers)

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Research

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11 pages, 2259 KiB

Open AccessArticle

Acute Liver Injury after CCl₄ Administration Is Independent of Smad7 Expression in Myeloid Cells

by Jessica Endig, Ludmilla Unrau, Paulina Sprezyna, Sebasting Rading, Meliha Karsak, Diane Goltz, Lukas C. Heukamp, Gisa Tiegs and Linda Diehl

Int. J. Mol. Sci. 2019, 20(22), 5528; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20225528 - 06 Nov 2019

Cited by 9 | Viewed by 3018

Abstract

Myeloid cells are essential for the initiation and termination of innate and adaptive immunity that create homeostasis in the liver. Smad7 is an inhibitor of the transforming growth factor β (TGF-β) signaling pathway, which regulates inflammatory cellular processes. Knockdown of Smad7 in hepatocytes has been shown to promote liver fibrosis, but little is known about the effects of Smad7 in myeloid cells during inflammatory responses in the liver. Using mice with a myeloid-specific knockdown of Smad7 (LysM-Cre Smad7^fl/fl), we investigated the impact of Smad7 deficiency in myeloid cells on liver inflammation and regeneration using the well-established model of CCl₄-mediated liver injury. Early (24/48 h) and late (7 d) time points were analyzed. We found that CCl₄ induces severe liver injury, with elevated serum ALT levels, centrilobular and periportal necrosis, infiltrating myeloid cells and an increase of inflammatory cytokines in the liver. Furthermore, as expected, inflammation peaked at 24 h and subsided after 7 d. However, the knockdown of Smad7 in myeloid cells did not affect any of the investigated parameters in the CCl₄-treated animals. In summary, our results suggest that the inhibition of TGF-β signaling via Smad7 expression in myeloid cells is dispensable for the induction and control of acute CCl₄-induced liver injury. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

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20 pages, 5087 KiB

Open AccessArticle

Hepatic Stellate Cells Enhance Liver Cancer Progression by Inducing Myeloid-Derived Suppressor Cells through Interleukin-6 Signaling

by Ching-Chuan Hsieh, Chien-Hui Hung, Meihua Chiang, Yu-Chin Tsai and Jie-Teng He

Int. J. Mol. Sci. 2019, 20(20), 5079; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205079 - 13 Oct 2019

Cited by 38 | Viewed by 3230

Abstract

The tumor microenvironment, which consists of fibroblasts, smooth muscle cells, endothelial cells, immune cells, epithelial cells, and extracellular matrices, plays a crucial role in tumor progression. Hepatic stellate cells (HSCs), a class of unique liver stromal cells, participate in immunomodulatory activities by inducing the apoptosis of effector T-cells, generation of regulatory T-cells, and development of myeloid-derived suppressor cells (MDSCs) to achieve long-term survival of islet allografts. This study provides in vitro and in vivo evidences that HSCs induce the generation of MDSCs to promote hepatocellular carcinoma (HCC) progression through interleukin (IL)-6 secretion. HSC-induced MDSCs highly expressed inducible nitric oxide synthase (iNOS) and arginase 1 mRNA and presented potent inhibitory T-cell immune responses in the tumor environment. Wild-type HSC-induced MDSCs expressed lower levels of CD40, CD86, and MHC II, and a higher level of B7-H1 surface molecules, as well as increased the production of iNOS and arginase I compared with MDSCs induced by IL-6-deficient HSCs in vitro. A murine-transplanted model of the liver tumor showed that HCCs cotransplanted with HSCs could significantly enhance the tumor area and detect more MDSCs compared with HCCs alone or HCCs cotransplanted with HSCs lacking IL-6. In conclusion, the results indicated that MDSCs are induced mainly by HSCs through IL-6 signaling and produce inhibitory enzymes to reduce T-cell immunity and then promote HCC progression within the tumor microenvironment. Therapies targeting the pathway involved in MDSC production or its immune-modulating pathways can serve as an alternative immunotherapy for HCC. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

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9 pages, 1857 KiB

Open AccessArticle

Whole Body Vibration-Induced Omental Macrophage Polarization and Fecal Microbiome Modification in a Murine Model

by Jack C. Yu, Vanessa L. Hale, Hesam Khodadadi and Babak Baban

Int. J. Mol. Sci. 2019, 20(13), 3125; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20133125 - 26 Jun 2019

Cited by 11 | Viewed by 26640

Abstract

Human nutrient metabolism, developed millions of years ago, is anachronistic. Adaptive features that offered survival advantages are now great liabilities. The current dietary pattern, coupled with massively reduced physical activities, causes an epidemic of obesity and chronic metabolic diseases, such as type 2 diabetes mellitus. Chronic inflammation is a major contributing factor to the initiation and progression of most metabolic and cardiovascular diseases. Among all components of an innate immune system, due to their dual roles as phagocytic as well as antigen-presenting cells, macrophages play an important role in the regulation of inflammatory responses, affecting the body’s microenvironment and homeostasis. Earlier studies have established the beneficial, anti-inflammatory effects of whole body vibration (WBV) as a partial exercise mimetic, including reversing the effects of glucose intolerance and hepatic steatosis. Here for the first time, we describe potential mechanisms by which WBV may improve metabolic status and ameliorate the adverse consequences through macrophage polarization and altering the fecal microbiome. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

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Review

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14 pages, 801 KiB

Open AccessReview

Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies

by Giuseppe Alberto Palumbo, Nunziatina Laura Parrinello, Cesarina Giallongo, Emanuele D’Amico, Aurora Zanghì, Fabrizio Puglisi, Concetta Conticello, Annalisa Chiarenza, Daniele Tibullo, Francesco Di Raimondo and Alessandra Romano

Int. J. Mol. Sci. 2019, 20(21), 5459; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215459 - 01 Nov 2019

Cited by 18 | Viewed by 3368

Abstract

In the era of novel agents and immunotherapies in solid and liquid tumors, there is an emerging need to understand the cross-talk between the neoplastic cells, the host immune system, and the microenvironment to mitigate proliferation, survival, migration and resistance to drugs. In the microenvironment of hematological tumors there are cells belonging to the normal bone marrow, extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and neoplastic cells themselves. In this context, myeloid suppressor cells are an emerging sub-population of regulatory myeloid cells at different stages of differentiation involved in cancer progression and chronic inflammation. In this review, monocytic myeloid derived suppressor cells and their potential clinical implications are discussed to give a comprehensive vision of their contribution to lymphoproliferative and myeloid disorders. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

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12 pages, 219 KiB

Open AccessReview

Delineating Pro-Angiogenic Myeloid Cells in Cancer Therapy

by Benjamin W. Johnson, Bhagelu R. Achyut, Sadanand Fulzele, Ashis K. Mondal, Ravindra Kolhe and Ali S. Arbab

Int. J. Mol. Sci. 2018, 19(9), 2565; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19092565 - 29 Aug 2018

Cited by 9 | Viewed by 2900

Abstract

Recent evidence suggests that myeloid cells are critical in cancer development and therapy resistance processes. Pharmacological targeting of tumor-associated myeloid cells is an emerging approach among upcoming immune therapies. Surprisingly, myeloid cells are heterogeneous, including a subset of the myeloid cell displaying angiogenic properties in solid tumors. There is an urgent need to delineate angiogenic myeloid cell populations in order to facilitate specific targeting of protumor myeloid cells among heterogeneous pool. This review article is intended to compile all the relevant information in the literature for improved understanding of angiogenic myeloid cells and their role in tumor refractoriness to cancer therapy. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

22 pages, 1014 KiB

Open AccessReview

Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ Transplantation

by Tsukasa Nakamura and Hidetaka Ushigome

Int. J. Mol. Sci. 2018, 19(8), 2357; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms19082357 - 10 Aug 2018

Cited by 38 | Viewed by 4886

Abstract

Regulation of allo-immune responses is proposed as a topic for investigation in the current field of organ transplantation. As a regulator, regulatory T cells (Tregs) have received attention due to their ability to control allograft rejection. Concurrently, however, the independent action of Tregs is not enough to achieve tolerance status in many situations. Meanwhile, as a multi-functional regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances. Furthermore, the importance of a crosstalk between MDSCs and natural killer T cells to induce tolerance has been reported. Thus, orchestration between MDSCs, myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light on achieving allogeneic tolerance. Here, we review the current knowledge in terms of immunological regulatory function displayed by MDSCs in the context of organ transplantation. Ideal control of MDSCs would lead to a reduction of allograft rejection and subsequent long-term allograft acceptance. Full article

(This article belongs to the Special Issue Myeloid Cells: Multi-Functional Regulators of Immune Suppression and Tumor Progression)

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