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Cancers
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Tumor-Associated Myeloid Cells
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Tumor-Associated Myeloid Cells

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 24413

Special Issue Editors

Prof. Dr. Takashi Matozaki

E-Mail Website
Guest Editor
Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan
Interests: cell-cell communication signals; cell adhesion; cancer; immunology
Prof. Dr. Timo K. van den Berg

E-Mail Website
Guest Editor
1. Sanquin Research, and Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, 1006 AD Amsterdam, Netherlands
2. Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, Netherlands
Interests: macrophages; granulocytes; infection; inflammation; atherosclerosis; cancer

Special Issue Information

Dear Colleagues,

The interaction of cancer cells with immune cells in the tumor microenvironment, particularly immunosurveillance by T cells against tumor cells, has recently been highlighted, and its therapeutic application by the use of PD-1/PD-L1-blocking antibodies or CAR-T has been well evaluated. By contrast, the importance of myeloid cells (e.g., dendritic cells, macrophages, and neutrophils) in the tumor microenvironment has been extensively investigated. Here in this Special Issue of Cancers, we attempt to overview the recent progress in the research for the roles of myeloid cells in the tumor microenvironment and their therapeutic application to cancer immunotherapy. In particular, the roles of various cell-surface molecules of myeloid cells that regulate innate and adaptive immunity will be extensively discussed in terms of immunosurveillance for tumor cells as well as potential therapeutic targets for cancers.

Prof. Dr. Takashi Matozaki
Prof. Dr. Timo K. van den Berg
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 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. Cancers 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 2900 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

  • dendritic cells
  • macrophages
  • neutrophils
  • myeloid cells
  • cancer immunity
  • innate immunity

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Published Papers (6 papers)

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Research

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17 pages, 3062 KiB  
Article
Phenotypic and Histological Distribution Analysis Identify Mast Cell Heterogeneity in Non-Small Cell Lung Cancer
by Edouard Leveque, Axel Rouch, Charlotte Syrykh, Julien Mazières, Laurent Brouchet, Salvatore Valitutti, Eric Espinosa and Fanny Lafouresse
Cancers 2022, 14(6), 1394; https://doi.org/10.3390/cancers14061394 - 9 Mar 2022
Cited by 14 | Viewed by 2434
Abstract
Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). However, MCs have been only barely characterized in studies focusing on global immune infiltrate phenotyping. Consequently, their role in cancer is still poorly understood. Furthermore, their prognosis value [...] Read more.
Mast cells (MCs) are multifaceted innate immune cells often present in the tumor microenvironment (TME). However, MCs have been only barely characterized in studies focusing on global immune infiltrate phenotyping. Consequently, their role in cancer is still poorly understood. Furthermore, their prognosis value is confusing since MCs have been associated with good and bad (or both) prognosis depending on the cancer type. In this pilot study performed on a surgical cohort of 48 patients with Non-Small Cell Lung Cancer (NSCLC), we characterized MC population within the TME and in matching non-lesional lung areas, by multicolor flow cytometry and confocal microscopy. Our results showed that tumor-associated MCs (TAMCs) harbor a distinct phenotype as compared with MCs present in non-lesional counterpart of the lung. Moreover, we found two TAMCs subsets based on the expression of CD103 (also named alphaE integrin). CD103+ TAMCs appeared more mature, more prone to interact with CD4+ T cells, and located closer to cancer cells than their CD103− counterpart. In spite of these characteristics, we did not observe a prognosis advantage of a high frequency of CD103+ TAMCs, while a high frequency of total TAMC correlated with better overall survival and progression free survival. Together, this study reveals that TAMCs constitute a heterogeneous population and indicates that MC subsets should be considered for patients’ stratification and management in future research. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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Review

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41 pages, 3266 KiB  
Review
Targeting the CD47-SIRPα Innate Immune Checkpoint to Potentiate Antibody Therapy in Cancer by Neutrophils
by Leonie M. Behrens, Timo K. van den Berg and Marjolein van Egmond
Cancers 2022, 14(14), 3366; https://doi.org/10.3390/cancers14143366 - 11 Jul 2022
Cited by 17 | Viewed by 6250
Abstract
In the past 25 years, a considerable number of therapeutic monoclonal antibodies (mAb) against a variety of tumor-associated antigens (TAA) have become available for the targeted treatment of hematologic and solid cancers. Such antibodies opsonize cancer cells and can trigger cytotoxic responses mediated [...] Read more.
In the past 25 years, a considerable number of therapeutic monoclonal antibodies (mAb) against a variety of tumor-associated antigens (TAA) have become available for the targeted treatment of hematologic and solid cancers. Such antibodies opsonize cancer cells and can trigger cytotoxic responses mediated by Fc-receptor expressing immune cells in the tumor microenvironment (TME). Although frequently ignored, neutrophils, which are abundantly present in the circulation and many cancers, have demonstrated to constitute bona fide effector cells for antibody-mediated tumor elimination in vivo. It has now also been established that neutrophils exert a unique mechanism of cytotoxicity towards antibody-opsonized tumor cells, known as trogoptosis, which involves Fc-receptor (FcR)-mediated trogocytosis of cancer cell plasma membrane leading to a lytic/necrotic type of cell death. However, neutrophils prominently express the myeloid inhibitory receptor SIRPα, which upon interaction with the ‘don’t eat me’ signal CD47 on cancer cells, limits cytotoxicity, forming a mechanism of resistance towards anti-cancer antibody therapeutics. In fact, tumor cells often overexpress CD47, thereby even more strongly restricting neutrophil-mediated tumor killing. Blocking the CD47-SIRPα interaction may therefore potentiate neutrophil-mediated antibody-dependent cellular cytotoxicity (ADCC) towards cancer cells, and various inhibitors of the CD47-SIRPα axis are now in clinical studies. Here, we review the role of neutrophils in antibody therapy in cancer and their regulation by the CD47-SIRPα innate immune checkpoint. Moreover, initial results of CD47-SIRPα blockade in clinical trials are discussed. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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16 pages, 1208 KiB  
Review
The Role of Type-2 Conventional Dendritic Cells in the Regulation of Tumor Immunity
by Yasuyuki Saito, Satomi Komori, Takenori Kotani, Yoji Murata and Takashi Matozaki
Cancers 2022, 14(8), 1976; https://doi.org/10.3390/cancers14081976 - 13 Apr 2022
Cited by 35 | Viewed by 5031
Abstract
Conventional dendritic cells (cDCs) orchestrate immune responses to cancer and comprise two major subsets: type-1 cDCs (cDC1s) and type-2 cDCs (cDC2s). Compared with cDC1s, which are dedicated to the activation of CD8+ T cells, cDC2s are ontogenically and functionally heterogeneous, with their [...] Read more.
Conventional dendritic cells (cDCs) orchestrate immune responses to cancer and comprise two major subsets: type-1 cDCs (cDC1s) and type-2 cDCs (cDC2s). Compared with cDC1s, which are dedicated to the activation of CD8+ T cells, cDC2s are ontogenically and functionally heterogeneous, with their main function being the presentation of exogenous antigens to CD4+ T cells for the initiation of T helper cell differentiation. cDC1s play an important role in tumor-specific immune responses through cross-presentation of tumor-derived antigens for the priming of CD8+ T cells, whereas little is known of the role of cDC2s in tumor immunity. Recent studies have indicated that human cDC2s can be divided into at least two subsets and have implicated these cells in both anti- and pro-tumoral immune responses. Furthermore, the efficacy of cDC2-based vaccines as well as cDC2-targeted therapeutics has been demonstrated in both mouse models and human patients. Here we summarize current knowledge about the role of cDC2s in tumor immunity and address whether these cells are beneficial in the context of antitumor immune responses. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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13 pages, 2275 KiB  
Review
Coordinated Regulation of Myeloid-Derived Suppressor Cells by Cytokines and Chemokines
by Ru Li, Mousumi Beto Mukherjee and Jun Lin
Cancers 2022, 14(5), 1236; https://doi.org/10.3390/cancers14051236 - 27 Feb 2022
Cited by 15 | Viewed by 2615
Abstract
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that impair immune cell functions and promote tumor progression. Mounting evidence indicates that cytokines and chemokines in the tumor microenvironment alter MDSCs. Various cytokines and chemokines are involved in MDSC production, their infiltration into tumors, [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that impair immune cell functions and promote tumor progression. Mounting evidence indicates that cytokines and chemokines in the tumor microenvironment alter MDSCs. Various cytokines and chemokines are involved in MDSC production, their infiltration into tumors, and their exertion of suppressive functions. Here, we consider those cytokines, chemokines, and MDSCs as an intricately connected, complex system and we focus on how tumors manipulate the MDSCs through various cytokines and chemokines. We also discuss treatment capitalizing on cytokines/chemokine signaling aimed at combating the potent immunosuppressive activities of MDSCs to improve disease outcomes. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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17 pages, 1144 KiB  
Review
Role of Tumor-Associated Neutrophils in the Molecular Carcinogenesis of the Lung
by Elisabeth Taucher, Valentin Taucher, Nicole Fink-Neuboeck, Joerg Lindenmann and Freyja-Maria Smolle-Juettner
Cancers 2021, 13(23), 5972; https://doi.org/10.3390/cancers13235972 - 27 Nov 2021
Cited by 12 | Viewed by 2421
Abstract
Tumorigenesis is largely influenced by accompanying inflammation. Myeloid cells account for a significant proportion of pro-inflammatory cells within the tumor microenvironment. All steps of tumor formation and progression, such as the suppression of adaptive immune response, angio- and lymphangiogenesis, and the remodeling of [...] Read more.
Tumorigenesis is largely influenced by accompanying inflammation. Myeloid cells account for a significant proportion of pro-inflammatory cells within the tumor microenvironment. All steps of tumor formation and progression, such as the suppression of adaptive immune response, angio- and lymphangiogenesis, and the remodeling of the tumor stroma, are to some degree influenced by tumor-associated immune cells. Tumor-associated neutrophils (TANs), together with tumor-associated macrophages and myeloid-derived suppressor cells, count among tumor-associated myeloid cells. Still, the exact molecular mechanisms underlying the tumorigenic effects of TANs have not been investigated in detail. With this review of the literature, we aim to give an overview of the current data on TANs, with a special focus on lung cancer. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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25 pages, 2578 KiB  
Review
Heterogeneous Myeloid Cells in Tumors
by Aixia Dou and Jing Fang
Cancers 2021, 13(15), 3772; https://doi.org/10.3390/cancers13153772 - 27 Jul 2021
Cited by 33 | Viewed by 4709
Abstract
Accumulating studies highlight a critical role of myeloid cells in cancer biology and therapy. The myeloid cells constitute the major components of tumor microenvironment (TME). The most studied tumor-associated myeloid cells (TAMCs) include monocytes, tumor-associated macrophages (TAMs), dendritic cells (DCs), cancer-related circulating neutrophils, [...] Read more.
Accumulating studies highlight a critical role of myeloid cells in cancer biology and therapy. The myeloid cells constitute the major components of tumor microenvironment (TME). The most studied tumor-associated myeloid cells (TAMCs) include monocytes, tumor-associated macrophages (TAMs), dendritic cells (DCs), cancer-related circulating neutrophils, tumor-associated neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs). These heterogenous myeloid cells perform pro-tumor or anti-tumor function, exerting complex and even opposing effects on all stages of tumor development, such as malignant clonal evolution, growth, survival, invasiveness, dissemination and metastasis of tumor cells. TAMCs also reshape TME and tumor vasculature to favor tumor development. The main function of these myeloid cells is to modulate the behavior of lymphocytes, forming immunostimulatory or immunosuppressive TME cues. In addition, TAMCs play a critical role in modulating the response to cancer therapy. Targeting TAMCs is vigorously tested as monotherapy or in combination with chemotherapy or immunotherapy. This review briefly introduces the TAMC subpopulations and their function in tumor cells, TME, angiogenesis, immunomodulation, and cancer therapy. Full article
(This article belongs to the Special Issue Tumor-Associated Myeloid Cells)
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