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Immunoregulation Within the Tumor Microenvironment: Special Emphasis on Macrophages and NK Cells

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 2771

Special Issue Editor

Prof. Dr. Walter Fiedler

E-Mail Website
Guest Editor
Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Interests: acute leukemia; phase 1 clinical studies; translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The tumor microenvironment (TME) has a major impact on solid and hematological tumors as well as on the immune system itself. It is still poorly understood which complex immunological and molecular mechanisms control these changes? In this Special Issue, we aim to collate papers which investigate mechanisms leading to functional changes in tumor-associated immune cell subsets such as T cells, NK cells, or macrophages within the TME. A focus here will be on new immunological target structures, transcription factors, and molecular pathways that have the therapeutic potential to restore the function of immune cells. Based on the current state of research, it seems particularly promising to test combined therapeutic approaches.

Prof. Dr. Walter Fiedler
Guest Editor

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.

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Keywords

  • microenvironment
  • macrophages
  • dendritic cells
  • NK cells
  • immune cells
  • MSCs

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Published Papers (2 papers)

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Research

19 pages, 11038 KiB  
Article
YKL40/Integrin β4 Axis Induced by the Interaction between Cancer Cells and Tumor-Associated Macrophages Is Involved in the Progression of High-Grade Serous Ovarian Carcinoma
by Keitaro Yamanaka, Yu-ichiro Koma, Satoshi Urakami, Ryosuke Takahashi, Satoshi Nagamata, Masaki Omori, Rikuya Torigoe, Hiroki Yokoo, Takashi Nakanishi, Nobuaki Ishihara, Shuichi Tsukamoto, Takayuki Kodama, Mari Nishio, Manabu Shigeoka, Hiroshi Yokozaki and Yoshito Terai
Int. J. Mol. Sci. 2024, 25(19), 10598; https://doi.org/10.3390/ijms251910598 - 1 Oct 2024
Viewed by 954
Abstract
Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor–stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, [...] Read more.
Macrophages in the tumor microenvironment, termed tumor-associated macrophages (TAMs), promote the progression of various cancer types. However, many mechanisms related to tumor–stromal interactions in epithelial ovarian cancer (EOC) progression remain unclear. High-grade serous ovarian carcinoma (HGSOC) is the most malignant EOC subtype. Herein, immunohistochemistry was performed on 65 HGSOC tissue samples, revealing that patients with a higher infiltration of CD68+, CD163+, and CD204+ macrophages had a poorer prognosis. We subsequently established an indirect co-culture system between macrophages and EOC cells, including HGSOC cells. The co-cultured macrophages showed increased expression of the TAM markers CD163 and CD204, and the co-cultured EOC cells exhibited enhanced proliferation, migration, and invasion. Cytokine array analysis revealed higher YKL40 secretion in the indirect co-culture system. The addition of YKL40 increased proliferation, migration, and invasion via extracellular signal-regulated kinase (Erk) signaling in EOC cells. The knockdown of integrin β4, one of the YKL40 receptors, suppressed YKL40-induced proliferation, migration, and invasion, as well as Erk phosphorylation in some EOC cells. Database analysis showed that high-level expression of YKL40 and integrin β4 correlated with a poor prognosis in patients with serous ovarian carcinoma. Therefore, the YKL40/integrin β4 axis may play a role in ovarian cancer progression. Full article
(This article belongs to the Special Issue Immunoregulation Within the Tumor Microenvironment: Special Emphasis on Macrophages and NK Cells)
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14 pages, 3660 KiB  
Article
Neutrophil-like Monocytes Increase in Patients with Colon Cancer and Induce Dysfunctional TIGIT+ NK Cells
by Alessia Calabrò, Fabiana Drommi, Giacomo Sidoti Migliore, Gaetana Pezzino, Grazia Vento, José Freni, Gregorio Costa, Riccardo Cavaliere, Irene Bonaccorsi, Mariagrazia Sionne, Stefania Nigro, Giuseppe Navarra, Guido Ferlazzo, Claudia De Pasquale and Stefania Campana
Int. J. Mol. Sci. 2024, 25(15), 8470; https://doi.org/10.3390/ijms25158470 - 2 Aug 2024
Viewed by 1144
Abstract
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of immune cells including granulocytic (CD14neg/CD15+/HLA-DRneg) and monocytic subtypes (CD14+/CD15neg/HLA-DRneg). In the present study, we found a population of monocytes expressing the granulocyte marker CD15 that significantly increased in both peripheral blood (PB) and tumoral [...] Read more.
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of immune cells including granulocytic (CD14neg/CD15+/HLA-DRneg) and monocytic subtypes (CD14+/CD15neg/HLA-DRneg). In the present study, we found a population of monocytes expressing the granulocyte marker CD15 that significantly increased in both peripheral blood (PB) and tumoral tissues of patients with colorectal cancer (CRC). Further phenotypical analysis confirmed the granulocytic-like features of this monocyte subpopulation that is associated with an increase in granulocyte–monocyte precursors (GMPs) in the PB of these patients (pts). Mechanistically, this granulocyte-like monocyte population suppressed NK cell activity by inducing TIGIT and engaging NKp30. Accordingly, an increased frequency of TIGIT+ NK cells with impaired functions was found in both the PB and tumoral tissue of CRC pts. Collectively, we provided new mechanistic explanations for tumor immune escape occurring in CRC by showing the increase in this new kind of MDSC, in both PB and CRC tissue, which is able to significantly impair the effector functions of NK cells, thereby representing a potential therapeutic target for cancer immunotherapy. Full article
(This article belongs to the Special Issue Immunoregulation Within the Tumor Microenvironment: Special Emphasis on Macrophages and NK Cells)
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