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Article: Revealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas

TitleRevealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas
Authors
KeywordsEGFR
Glioma
Immune suppression
TAM-SPP1
Tumor-associated macrophages
Issue Date21-Mar-2024
PublisherBioMed Central
Citation
Cell & Bioscience, 2024, v. 14, n. 1 How to Cite?
Abstract

Background

Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients.

Results

Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (EGFR) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, EGFR status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients.

Conclusion

Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients.


Persistent Identifierhttp://hdl.handle.net/10722/342104
ISSN
2023 Impact Factor: 6.1
2023 SCImago Journal Rankings: 1.836
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTang, Wenshu-
dc.contributor.authorLo, Cario W S-
dc.contributor.authorMa, Wei-
dc.contributor.authorChu, Annie T W-
dc.contributor.authorTong, Amy H Y-
dc.contributor.authorChung, Brian H Y-
dc.date.accessioned2024-04-02T08:25:36Z-
dc.date.available2024-04-02T08:25:36Z-
dc.date.issued2024-03-21-
dc.identifier.citationCell & Bioscience, 2024, v. 14, n. 1-
dc.identifier.issn2045-3701-
dc.identifier.urihttp://hdl.handle.net/10722/342104-
dc.description.abstract<h3>Background</h3><p>Glioma is a highly heterogeneous brain tumor categorized into World Health Organization (WHO) grades 1–4 based on its malignancy. The suppressive immune microenvironment of glioma contributes significantly to unfavourable patient outcomes. However, the cellular composition and their complex interplays within the glioma environment remain poorly understood, and reliable prognostic markers remain elusive. Therefore, in-depth exploration of the tumor microenvironment (TME) and identification of predictive markers are crucial for improving the clinical management of glioma patients.</p><h3>Results</h3><p>Our analysis of single-cell RNA-sequencing data from glioma samples unveiled the immunosuppressive role of tumor-associated macrophages (TAMs), mediated through intricate interactions with tumor cells and lymphocytes. We also discovered the heterogeneity within TAMs, among which a group of suppressive TAMs named TAM-SPP1 demonstrated a significant association with Epidermal Growth Factor Receptor (<em>EGFR</em>) amplification, impaired T cell response and unfavourable patient survival outcomes. Furthermore, by leveraging genomic and transcriptomic data from The Cancer Genome Atlas (TCGA) dataset, two distinct molecular subtypes with a different constitution of TAMs, <em>EGFR</em> status and clinical outcomes were identified. Exploiting the molecular differences between these two subtypes, we developed a four-gene-based prognostic model. This model displayed strong associations with an elevated level of suppressive TAMs and could be used to predict anti-tumor immune response and prognosis in glioma patients.</p><h3>Conclusion</h3><p>Our findings illuminated the molecular and cellular mechanisms that shape the immunosuppressive microenvironment in gliomas, providing novel insights into potential therapeutic targets. Furthermore, the developed prognostic model holds promise for predicting immunotherapy response and assisting in more precise risk stratification for glioma patients.</p>-
dc.languageeng-
dc.publisherBioMed Central-
dc.relation.ispartofCell & Bioscience-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEGFR-
dc.subjectGlioma-
dc.subjectImmune suppression-
dc.subjectTAM-SPP1-
dc.subjectTumor-associated macrophages-
dc.titleRevealing the role of SPP1+ macrophages in glioma prognosis and therapeutic targeting by investigating tumor-associated macrophage landscape in grade 2 and 3 gliomas-
dc.typeArticle-
dc.identifier.doi10.1186/s13578-024-01218-4-
dc.identifier.scopuseid_2-s2.0-85188248058-
dc.identifier.volume14-
dc.identifier.issue1-
dc.identifier.eissn2045-3701-
dc.identifier.isiWOS:001190584300001-
dc.identifier.issnl2045-3701-

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