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Special Issue "Macrophages in the Glioblastoma Tumor Microenvironment"

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

Deadline for manuscript submissions: closed (15 October 2021).

Special Issue Editor

Dr. Salvatore Coniglio
E-Mail Website
Guest Editor
New Jersey Center for Science, Technology and Mathematics, Kean University, Union, NJ, USA
Interests: cancer; glioblastoma; invasion; macrophages; microenvironment; microglia; chemokines; metastasis

Special Issue Information

Dear Colleagues,

Glioblastoma (GBM) is one of the deadliest human cancers, with a median survival of 12 months from time of diagnosis. Several factors contribute to the malignancy of GBM, including a high degree of local invasiveness, resistance to chemotherapy, and the presence of immunosuppressive cells within the tumor microenvironment. It is known that GBM infiltrating macrophages (GIMs) are prevalent within advanced tumors, in many cases comprising up to 33% of the tumor mass. Substantial evidence demonstrates that these GIMs are responsible for actively promoting the malignant progression of GBM. In this Special Issue, we focus on the molecular mechanisms by which GBM cells recruit and modulate macrophage behavior within the tumor microenvironment. Emphasis is on the roles of colony-stimulating factors (CSF-1, CSF-2/GMCSF) and chemokines in this process.

Dr. Salvatore Coniglio
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 papers will be 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

  • glioblastoma
  • microglia
  • macrophages
  • myeloid
  • microenvironment
  • chemokines
  • CSF-1 (colony stimulating factor-1)
  • GMCSF (granulocyte-monocyte colony stimulating factor)

Published Papers (2 papers)

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Article
Hijacking Sexual Immuno-Privilege in GBM—An Immuno-Evasion Strategy
Int. J. Mol. Sci. 2021, 22(20), 10983; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222010983 - 12 Oct 2021
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Abstract
Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to ‘Self’ tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive [...] Read more.
Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to ‘Self’ tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing ≈900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient’s reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression. Full article
(This article belongs to the Special Issue Macrophages in the Glioblastoma Tumor Microenvironment)
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Review

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Review
Macrophages/Microglia in the Glioblastoma Tumor Microenvironment
Int. J. Mol. Sci. 2021, 22(11), 5775; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115775 - 28 May 2021
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Abstract
The complex interaction between glioblastoma and its microenvironment has been recognized for decades. Among various immune profiles, the major population is tumor-associated macrophage, with microglia as its localized homolog. The present definition of such myeloid cells is based on a series of cell [...] Read more.
The complex interaction between glioblastoma and its microenvironment has been recognized for decades. Among various immune profiles, the major population is tumor-associated macrophage, with microglia as its localized homolog. The present definition of such myeloid cells is based on a series of cell markers. These good sentinel cells experience significant changes, facilitating glioblastoma development and protecting it from therapeutic treatments. Huge, complicated mechanisms are involved during the overall processes. A lot of effort has been dedicated to crack the mysterious codes in macrophage/microglia recruiting, activating, reprogramming, and functioning. We have made our path. With more and more key factors identified, a lot of new therapeutic methods could be explored to break the ominous loop, to enhance tumor sensitivity to treatments, and to improve the prognosis of glioblastoma patients. However, it might be a synergistic system rather than a series of clear, stepwise events. There are still significant challenges before the light of truth can shine onto the field. Here, we summarize recent advances in this field, reviewing the path we have been on and where we are now. Full article
(This article belongs to the Special Issue Macrophages in the Glioblastoma Tumor Microenvironment)
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