{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T14:56:57Z","timestamp":1780930617469,"version":"3.54.1"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Glioblastoma (GBM) is a very aggressive form of cancer affecting the central nervous system. Although it occurs almost exclusively in the brain, glioblastoma can also appear in the brainstem, cerebellum, and spinal cord. It is characterized by high rates of proliferation, invasion, and necrosis. Moreover, GBM is a highly vascularized tumor and presents resistance to therapy. Recent data indicate that GBM cells are surrounded by a microenvironment (TME) which includes a complex network constituted of cellular\/extracellular components and vessels able to influence both tumor growth and angiogenesis. In this retrospective study, we evaluated 30 bioptic specimens of adult patients diagnosed with IDH1 wild type GBM taken at the time of the first diagnosis. Each section has been divided into two experimental zones: the tumor side and the healthy surrounding tissue. We performed a series of immunohistochemical stainings with the purpose of evaluating the presence of total and M2 macrophages, CD4+-, CD8+-lymphocytes, and CD34+ microvessels. In addition, we have also evaluated the percentage of cells expressing bcl6 and p53 to determine any possible correlations with TME. Our data showed a significant increase in the total and M2 type macrophages, of CD4+ and CD8+ lymphocytes, and of CD34+ microvessels in the tumoral area respective to the healthy zone. We also confirmed our previous data showing the higher number of p53 and BCL6+ cells in the tumor area with a positive correlation between BCL6 and CD34+ microvessels. In conclusion, the data that came from this work support the important role played by microenvironment components in GBM progression. These results could contribute to the generation of new specific therapies useful in preventing GBM progression.<\/jats:p>","DOI":"10.3390\/cells12010011","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T01:32:53Z","timestamp":1671586373000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Tumor Microenvironment and Microvascular Density in Human Glioblastoma"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-5406","authenticated-orcid":false,"given":"Roberto","family":"Tamma","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-3545","authenticated-orcid":false,"given":"Giuseppe","family":"Ingravallo","sequence":"additional","affiliation":[{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiziana","family":"Annese","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, 70124 Bari, Italy"},{"name":"Department of Medicine and Surgery, Libera Universit\u00e0 del Mediterraneo (LUM) Giuseppe Degennaro University, 70010 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-1201","authenticated-orcid":false,"given":"Antonio","family":"d\u2019Amati","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, 70124 Bari, Italy"},{"name":"Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loredana","family":"Lorusso","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4768-8431","authenticated-orcid":false,"given":"Domenico","family":"Ribatti","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neuroscience, University of Bari Medical School, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"iii1","DOI":"10.1093\/neuonc\/noab200","article-title":"CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014\u20132018","volume":"23","author":"Ostrom","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"71330","DOI":"10.18632\/oncotarget.11114","article-title":"Circulating tumor cell is a common property of brain glioma and promotes the monitoring system","volume":"7","author":"Gao","year":"2016","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/BF00294647","article-title":"Monocyte subpopulations in human gliomas: Expression of Fc and complement receptors and correlation with tumor proliferation","volume":"80","author":"Morimura","year":"1990","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/j.humpath.2013.03.013","article-title":"Astrocytoma grade IV (glioblastoma multiforme) displays 3 subtypes with unique expression profiles of intermediate filament proteins","volume":"44","author":"Skalli","year":"2013","journal-title":"Hum. 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