{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:46:35Z","timestamp":1781534795327,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:00:00Z","timestamp":1768089600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Significant heterogeneity in the immune microenvironment of Glioblastoma, IDH\u2010wildtype (GBM), has been reported, necessitating a standardized approach to evaluate immune infiltration in the context of emerging immunotherapies. To address this, we developed and validated a standardized immunohistochemistry\u2010based scoring system for quantifying immune cell infiltration in formalin\u2010fixed, paraffin\u2010embedded (FFPE) tissue. Paired primary and recurrent GBM specimens from 20 adult patients were labeled for CD3, CD8, CD45, CD68, and PD\u20101, and scored across six anatomical regions, including intra\u2010 and peritumoral, meningeal, and normal brain areas. The scoring system demonstrated excellent interrater (ICC\u2009=\u20090.932) and intrarater (ICC\u2009=\u20090.953) reliability. CD68+ and CD45+ cells were most numerous across all regions. CD3+ and CD8+ cells concentrated more in the perivascular area rather than within the parenchyma. No significant differences in immune infiltration were observed between primary and recurrent GBM. Cox proportional\u2010hazards analysis showed worse survival with higher CD8+ and CD45+ infiltration in primary GBM, and higher CD45+ and CD68+ infiltration in recurrent GBM. In conclusion, we propose a feasible, cost\u2010efficient, and robust method to assess immune infiltration on FFPE material, enabling standardized comparison of inflammation, with applications for ongoing clinical trials.<\/jats:p>","DOI":"10.1111\/apm.70143","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T07:12:57Z","timestamp":1768201977000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune Cell Infiltration in Primary and Recurrent Glioblastoma,\n                    <scp>IDH<\/scp>\n                    \u2010Wild Type: Validation of an Immunohistochemistry\u2010Based Scoring System for Research and Clinical Practice"],"prefix":"10.1111","volume":"134","author":[{"given":"Leontien","family":"Verlinden","sequence":"first","affiliation":[{"name":"Experimental Pathology (EXPA) Vrije Universiteit Brussel (VUB)  Brussels Belgium"},{"name":"Department of Pathology Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Michotte","sequence":"additional","affiliation":[{"name":"Department of Pathology Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Cools","sequence":"additional","affiliation":[{"name":"Vrije Universiteit Brussel (VUB)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Locy","sequence":"additional","affiliation":[{"name":"Experimental Pathology (EXPA) Vrije Universiteit Brussel (VUB)  Brussels Belgium"},{"name":"Department of Pathology Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramses","family":"Forsyth","sequence":"additional","affiliation":[{"name":"Experimental Pathology (EXPA) Vrije Universiteit Brussel (VUB)  Brussels Belgium"},{"name":"Department of Pathology Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Duerinck","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Neyns","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Laboratory for Medical and Molecular Oncology (LMMO), Translational Oncology Research Center (TORC) Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Brock","sequence":"additional","affiliation":[{"name":"Experimental Pathology (EXPA) Vrije Universiteit Brussel (VUB)  Brussels Belgium"},{"name":"Department of Pathology Universitair Ziekenhuis Brussel (UZ Brussel)  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noab106"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00090-5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28836"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13153721"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5681"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2018.08.133"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm10030112"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdaa083"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.04.038"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.029"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00154"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.820673"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.52176","article-title":"Understanding the Glioblastoma Immune Microenvironment as Basis for the Development of New Immunotherapeutic Strategies","volume":"9","author":"Pombo Antunes A. 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