{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:14:19Z","timestamp":1788149659516,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010081","name":"Conseil R\u00e9gional de La R\u00e9union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010081","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Glioblastomas (GBM), IDH\u2010wildtype, are highly aggressive brain tumors with poor prognosis and inter\u2010individual variability despite established prognostic factors such as age, performance status, and MGMT promoter (MGMTp) methylation. Increasing evidence highlights the role of the tumor microenvironment (TME) in GBM progression. The complement system, a key component of innate immunity, can influence tumor growth and immune regulation through the generation of the anaphylatoxin C3a and the activation of its receptor, C3aR. While C3a\/C3aR signaling has been associated with various outcomes in several malignancies, its prognostic relevance in GBM remains poorly defined. This study investigated the expression of C3aR in human IDH\u2010wildtype GBM and its association with clinicopathological features and overall survival. We retrospectively analyzed a cohort of 114 patients with IDH\u2010wildtype GBM. C3aR expression was assessed by immunohistochemistry and quantified using digital image analysis. C3aR expression was analyzed as a categorical variable using an outcome\u2010derived cutpoint (C3aR\u2010high and C3aR\u2010low) for exploratory purposes. Associations with clinical variables, including MGMTp methylation status, were evaluated. C3aR expression showed marked inter\u2010tumoral heterogeneity and was enriched among MGMTp\u2010methylated tumors (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004). Patients with C3aR\u2010high tumors exhibited improved overall survival (log\u2010rank\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033). In a multivariable Cox regression model including age, performance status, surgery type, and MGMTp methylation status, high C3aR expression remained independently associated with improved overall survival (HR 0.50, 95% CI 0.29\u20130.87,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.014). Tissue\u2010based and single\u2010cell analyses supported the association of C3aR with the myeloid\/macrophage compartment and heterogeneous macrophage phenotypes. These findings support a relationship between C3aR expression and the heterogeneous macrophage landscape of IDH\u2010wildtype GBM, while the survival association remains exploratory and requires independent validation.\n                  <\/jats:p>","DOI":"10.1111\/bpa.70141","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:27:16Z","timestamp":1788146836000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Complement receptor\n                    <scp>C3aR<\/scp>\n                    marks heterogeneous tumor\u2010associated macrophage states associated with improved survival in\n                    <scp>IDH<\/scp>\n                    \u2010wildtype glioblastoma"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1173-4687","authenticated-orcid":false,"given":"Marion","family":"Imara","sequence":"first","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco\u2010Immunologie (UR\u2010EPI) Universit\u00e9 et CHU de La R\u00e9union  Saint\u2010Denis France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7072-4571","authenticated-orcid":false,"given":"Yosra","family":"Bedoui","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"},{"name":"Tumoroth\u00e8que r\u00e9gionale de La R\u00e9union CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0926-4735","authenticated-orcid":false,"given":"Th\u00e9otime","family":"Pignolet","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Freppel","sequence":"additional","affiliation":[{"name":"Service de Neurochirurgie CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0846-3451","authenticated-orcid":false,"given":"Camille","family":"Brochard","sequence":"additional","affiliation":[{"name":"Service d'Anatomie et Cytologie Pathologiques CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Auguste","family":"Delattre","sequence":"additional","affiliation":[{"name":"Service d'oncologie m\u00e9dicale CHU de La R\u00e9union  Saint\u2010Pierre Cedex R\u00e9union France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Cappellen","sequence":"additional","affiliation":[{"name":"Service de Biologie des tumeurs\u2014Tumoroth\u00e8que CHU de Bordeaux  Pessac France"},{"name":"Bordeaux Institute of Oncology (BRIC), UMR 1312 Inserm Universit\u00e9 de Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1077-2496","authenticated-orcid":false,"given":"Luc","family":"Bauchet","sequence":"additional","affiliation":[{"name":"IGF University of Montpellier, CNRS, INSERM  Montpellier France"},{"name":"Department of Neurosurgery H\u00f4pital Gui de Chauliac, Montpellier University Medical Center  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-4901","authenticated-orcid":false,"given":"Mohamed","family":"Khettab","sequence":"additional","affiliation":[{"name":"Service d'oncologie m\u00e9dicale CHU de La R\u00e9union  Saint\u2010Pierre Cedex R\u00e9union France"},{"name":"IGF University of Montpellier, CNRS, INSERM  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-0665","authenticated-orcid":false,"given":"Franck","family":"Ah\u2010Pine","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Recherche en Pharmaco\u2010Immunologie (UR\u2010EPI) Universit\u00e9 et CHU de La R\u00e9union  Saint\u2010Denis France"},{"name":"Service d'Anatomie et Cytologie Pathologiques CHU de La R\u00e9union site SUD\u2010Saint\u2010Pierre  Saint\u2010Pierre Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"World Health Organization Classification of Tumours of the Central Nervous System [Internet]","author":"WHO Classification of Tumours Editorial 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