{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:33:50Z","timestamp":1792812830848,"version":"4.5.0"},"reference-count":72,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["PRIDE21\/16763386\/CANBIO2"],"award-info":[{"award-number":["PRIDE21\/16763386\/CANBIO2"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["C21\/BM\/15739125\/DIOMEDES"],"award-info":[{"award-number":["C21\/BM\/15739125\/DIOMEDES"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["PRIDE\/14254520\/I2TRON"],"award-info":[{"award-number":["PRIDE\/14254520\/I2TRON"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["INTER\/DFG\/17\/11583046"],"award-info":[{"award-number":["INTER\/DFG\/17\/11583046"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["P16\/BM\/11192868"],"award-info":[{"award-number":["P16\/BM\/11192868"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001866","name":"Fonds National de la Recherche Luxembourg","doi-asserted-by":"publisher","award":["C24\/BM\/18858278\/GRALL"],"award-info":[{"award-number":["C24\/BM\/18858278\/GRALL"]}],"id":[{"id":"10.13039\/501100001866","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","award":["7.8513.18\/7651720F"],"award-info":[{"award-number":["7.8513.18\/7651720F"]}],"id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is an aggressive and lethal brain tumor marked by profound local and systemic immune dysfunction. Despite evidence of peripheral immune impairment, the clinical relevance of these alterations for diagnostic or therapeutic purposes remains poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed multimodal single-cell profiling of peripheral blood mononuclear cells from a single-center cohort of treatment-na\u00efve GBM patients and healthy donors, integrating mass and flow cytometry with single-cell RNA-sequencing. Unsupervised clustering, pseudo-temporal trajectory analyses and cell\u2013cell communication inference were applied to map immune states and their interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      GBM blood profiles were characterized by heterogeneous changes in classical monocytes, encompassing expanded, reduced and unchanged subsets with distinct functional states, including antigen-presenting, interferon and metabolic programs. Additional myeloid adaptations included myeloid-derived suppressor cell (MDSC) expansion and loss of non-classical monocytes. Trajectory analyses identified a differentiation continuum, evolving from antigen-presenting to metabolic monocyte subsets, and positioning MDSCs as an intermediate state. Antigen\u2011presenting monocytes displayed tumor\u2011migratory, precursor\u2011like profiles that corresponded to tumor\u2011associated macrophages in public GBM datasets. Across subsets, circulating monocytes shared a \u201cGBM-classical monocytic signature\u201d characterized by low MHC class II expression, altered cell\u2013cell communication and upregulation of anti-inflammatory mediators, including\n                      <jats:italic>IL1R2<\/jats:italic>\n                      and\n                      <jats:italic>CD163<\/jats:italic>\n                      . Notably, complementary myeloid expression signatures were identified across patients, indicating distinct systemic immune phenotypes. In parallel, lymphocyte alterations included decreased proportions of CD4\n                      <jats:sup>+<\/jats:sup>\n                      T, natural killer (NK) and CD56\n                      <jats:sup>+<\/jats:sup>\n                      T cells, retaining relatively conserved activation profiles, exemplified by up-regulation of alarmins\n                      <jats:italic>S100A8\/S100A9<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings delineate systemic immune reprogramming in primary GBM, characterized by coordinated myeloid and lymphocyte alterations. The identification of circulating monocyte states with transcriptional continuity to the tumour microenvironment, alongside distinct patient-level systemic myeloid signatures, provides a framework for exploring peripheral blood as a source of immune biomarkers in GBM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-026-03964-3","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T12:33:39Z","timestamp":1784205219000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circulating immune profiling reveals impaired monocyte states and trajectories driving immunosuppression in glioblastoma"],"prefix":"10.1186","volume":"23","author":[{"given":"Andrea","family":"Scafidi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Kaoma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Cerella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Campus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamil","family":"Grzyb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakhtiyor","family":"Nosirov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frida","family":"Lind-Holm Mogensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliane","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul","family":"Da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Skupin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hertel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Berchem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Mittelbronn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Cosma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Melin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone P.","family":"Niclou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr V.","family":"Nazarov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Golebiewska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Poli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1230-061X","authenticated-orcid":false,"given":"Alessandro","family":"Michelucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"7","key":"3964_CR1","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1001\/jama.2023.0023","volume":"329","author":"LR Schaff","year":"2023","unstructured":"Schaff LR, Mellinghoff IK. Glioblastoma and other primary brain malignancies in adults: a review. JAMA. 2023;329(7):574\u201387.","journal-title":"JAMA"},{"issue":"3","key":"3964_CR2","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3390\/ijms21030689","volume":"21","author":"Y Pires-Afonso","year":"2020","unstructured":"Pires-Afonso Y, Niclou SP, Michelucci A. Revealing and harnessing tumour-associated microglia\/macrophage heterogeneity in glioblastoma. Int J Mol Sci. 2020;21(3):689.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"3964_CR3","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s13073-024-01321-8","volume":"16","author":"YA Yabo","year":"2024","unstructured":"Yabo YA, Moreno-Sanchez PM, Pires-Afonso Y, Kaoma T, Nosirov B, Scafidi A, et al. Glioblastoma-instructed microglia transition to heterogeneous phenotypic states with phagocytic and dendritic cell-like features in patient tumors and patient-derived orthotopic xenografts. Genome Med. 2024;16(1):51.","journal-title":"Genome Med"},{"issue":"2","key":"3964_CR4","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1158\/2326-6066.CIR-23-0211","volume":"12","author":"X Ran","year":"2024","unstructured":"Ran X, Zheng J, Chen L, Xia Z, Wang Y, Sun C, et al. Single-cell transcriptomics reveals the heterogeneity of the immune landscape of IDH-wild-type high-grade gliomas. Cancer Immunol Res. 2024;12(2):232\u201346.","journal-title":"Cancer Immunol Res"},{"key":"3964_CR5","doi-asserted-by":"publisher","first-page":"RP92678","DOI":"10.7554\/eLife.92678.2","volume":"12","author":"P Schmassmann","year":"2023","unstructured":"Schmassmann P, Roux J, Dettling S, Hogan S, Shekarian T, Martins TA, et al. Single-cell characterization of human GBM reveals regional differences in tumor-infiltrating leukocyte activation. Elife. 2023;12:RP92678.","journal-title":"Elife"},{"issue":"19","key":"3964_CR6","doi-asserted-by":"publisher","first-page":"5671","DOI":"10.1158\/0008-5472.CAN-16-0144","volume":"76","author":"AL Chang","year":"2016","unstructured":"Chang AL, Miska J, Wainwright DA, Dey M, Rivetta CV, Yu D, et al. CCL2 produced by the glioma microenvironment is essential for the recruitment of regulatory T cells and myeloid-derived suppressor cells. Cancer Res. 2016;76(19):5671\u201382.","journal-title":"Cancer Res"},{"issue":"1","key":"3964_CR7","doi-asserted-by":"publisher","first-page":"e163451","DOI":"10.1172\/JCI163451","volume":"133","author":"D Friedmann-Morvinski","year":"2023","unstructured":"Friedmann-Morvinski D, Hambardzumyan D. Monocyte-neutrophil entanglement in glioblastoma. J Clin Invest. 2023;133(1):e163451.","journal-title":"J Clin Invest"},{"issue":"8","key":"3964_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/s41577-020-00490-y","volume":"21","author":"F Veglia","year":"2021","unstructured":"Veglia F, Sanseviero E, Gabrilovich DI. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat Rev Immunol. 2021;21(8):485\u201398.","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"3964_CR9","doi-asserted-by":"publisher","first-page":"3629","DOI":"10.1093\/brain\/awaa343","volume":"143","author":"K Ayasoufi","year":"2020","unstructured":"Ayasoufi K, Pfaller CK, Evgin L, Khadka RH, Tritz ZP, Goddery EN, et al. Brain cancer induces systemic immunosuppression through release of non-steroid soluble mediators. Brain. 2020;143(12):3629\u201352.","journal-title":"Brain"},{"issue":"9","key":"3964_CR10","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1038\/s41591-018-0135-2","volume":"24","author":"P Chongsathidkiet","year":"2018","unstructured":"Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med. 2018;24(9):1459\u201368.","journal-title":"Nat Med"},{"issue":"1","key":"3964_CR11","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s13045-024-01544-7","volume":"17","author":"H Lin","year":"2024","unstructured":"Lin H, Liu C, Hu A, Zhang D, Yang H, Mao Y. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives. J Hematol Oncol. 2024;17(1):31.","journal-title":"J Hematol Oncol"},{"issue":"Suppl 4","key":"3964_CR12","doi-asserted-by":"publisher","first-page":"iv4","DOI":"10.1093\/noajnl\/vdaf006","volume":"7","author":"BJ Puviindran","year":"2025","unstructured":"Puviindran BJ, Wallace S, Ayasoufi K, Lerner E, Fecci PE. Within and beyond the tumor: mechanisms of glioblastoma-induced immunosuppression. Neuro-oncol Adv. 2025;7(Suppl 4):iv4\u201318.","journal-title":"Neuro-oncol Adv"},{"issue":"9","key":"3964_CR13","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1093\/neuonc\/now034","volume":"18","author":"PR Gielen","year":"2016","unstructured":"Gielen PR, Schulte BM, Kers-Rebel ED, Verrijp K, Bossman SA, Ter Laan M, et al. Elevated levels of polymorphonuclear myeloid-derived suppressor cells in patients with glioblastoma highly express S100A8\/9 and arginase and suppress T cell function. Neuro Oncol. 2016;18(9):1253\u201364.","journal-title":"Neuro Oncol"},{"key":"3964_CR14","doi-asserted-by":"publisher","first-page":"809826","DOI":"10.3389\/fimmu.2021.809826","volume":"12","author":"P Del Bianco","year":"2021","unstructured":"Del Bianco P, Pinton L, Magri S, Cane S, Masetto E, Basso D, et al. Myeloid diagnostic and prognostic markers of immune suppression in the blood of glioma patients. Front Immunol. 2021;12:809826.","journal-title":"Front Immunol"},{"issue":"1","key":"3964_CR15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/s13045-016-0272-3","volume":"9","author":"H Mostafa","year":"2016","unstructured":"Mostafa H, Pala A, Hogel J, Hlavac M, Dietrich E, Westhoff MA, et al. Immune phenotypes predict survival in patients with glioblastoma multiforme. J Hematol Oncol. 2016;9(1):77.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"3964_CR16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1038\/s41525-022-00348-3","volume":"8","author":"D Qi","year":"2023","unstructured":"Qi D, Geng Y, Cardenas J, Gu J, Yi SS, Huang JH, et al. Transcriptomic analyses of patient peripheral blood with hemoglobin depletion reveal glioblastoma biomarkers. NPJ Genom Med. 2023;8(1):2.","journal-title":"NPJ Genom Med"},{"issue":"9","key":"3964_CR17","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1002\/cyto.a.24359","volume":"99","author":"F Hedin","year":"2021","unstructured":"Hedin F, Konstantinou M, Cosma A. Data integration and visualization techniques for post-cytometric analysis of complex datasets. Cytometry A. 2021;99(9):930\u20138.","journal-title":"Cytometry A"},{"issue":"13","key":"3964_CR18","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","volume":"184","author":"Y Hao","year":"2021","unstructured":"Hao Y, Hao S, Andersen-Nissen E, Mauck WM 3rd, Zheng S, Butler A, et al. Integrated analysis of multimodal single-cell data. Cell. 2021;184(13):3573-87 e29.","journal-title":"Cell"},{"issue":"1","key":"3964_CR19","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","volume":"12","author":"S Jin","year":"2021","unstructured":"Jin S, Guerrero-Juarez CF, Zhang L, Chang I, Ramos R, Kuan CH, et al. Inference and analysis of cell-cell communication using Cell Chat. Nat Commun. 2021;12(1):1088.","journal-title":"Nat Commun"},{"issue":"1","key":"3964_CR20","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","volume":"20","author":"S Jin","year":"2025","unstructured":"Jin S, Plikus MV, Nie Q. Cell Chat for systematic analysis of cell-cell communication from single-cell transcriptomics. Nat Protoc. 2025;20(1):180\u2013219.","journal-title":"Nat Protoc"},{"issue":"18","key":"3964_CR21","doi-asserted-by":"publisher","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","volume":"32","author":"Z Gu","year":"2016","unstructured":"Gu Z, Eils R, Schlesner M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics. 2016;32(18):2847\u20139.","journal-title":"Bioinformatics"},{"issue":"21","key":"3964_CR22","doi-asserted-by":"publisher","first-page":"e122264","DOI":"10.1172\/jci.insight.122264","volume":"3","author":"TJ Alban","year":"2018","unstructured":"Alban TJ, Alvarado AG, Sorensen MD, Bayik D, Volovetz J, Serbinowski E, et al. Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis. JCI Insight. 2018;3(21):e122264.","journal-title":"JCI Insight"},{"issue":"1","key":"3964_CR23","doi-asserted-by":"publisher","first-page":"872","DOI":"10.1038\/s41467-024-45240-z","volume":"15","author":"M Andreatta","year":"2024","unstructured":"Andreatta M, Herault L, Gueguen P, Gfeller D, Berenstein AJ, Carmona SJ. Semi-supervised integration of single-cell transcriptomics data. Nat Commun. 2024;15(1):872.","journal-title":"Nat Commun"},{"issue":"5","key":"3964_CR24","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1097\/NEN.0000000000000183","volume":"74","author":"PR Gielen","year":"2015","unstructured":"Gielen PR, Schulte BM, Kers-Rebel ED, Verrijp K, Petersen-Baltussen HM, ter Laan M, et al. Increase in both CD14-positive and CD15-positive myeloid-derived suppressor cell subpopulations in the blood of patients with glioma but predominance of CD15-positive myeloid-derived suppressor cells in glioma tissue. J Neuropathol Exp Neurol. 2015;74(5):390\u2013400.","journal-title":"J Neuropathol Exp Neurol"},{"issue":"5","key":"3964_CR25","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1097\/SHK.0000000000001671","volume":"55","author":"DB Darden","year":"2021","unstructured":"Darden DB, Bacher R, Brusko MA, Knight P, Hawkins RB, Cox MC, et al. Single-Cell RNA-seq of Human Myeloid-Derived Suppressor Cells in Late Sepsis Reveals Multiple Subsets With Unique Transcriptional Responses: A Pilot Study. Shock. 2021;55(5):587\u201395.","journal-title":"Shock"},{"issue":"6","key":"3964_CR26","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1016\/j.cell.2020.08.001","volume":"182","author":"J Schulte-Schrepping","year":"2020","unstructured":"Schulte-Schrepping J, Reusch N, Paclik D, Bassler K, Schlickeiser S, Zhang B, et al. Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell. 2020;182(6):1419-40 e23.","journal-title":"Cell"},{"issue":"11","key":"3964_CR27","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1038\/nmeth.4463","volume":"14","author":"S Aibar","year":"2017","unstructured":"Aibar S, Gonzalez-Blas CB, Moerman T, Huynh-Thu VA, Imrichova H, Hulselmans G, et al. SCENIC: single-cell regulatory network inference and clustering. Nat Methods. 2017;14(11):1083\u20136.","journal-title":"Nat Methods"},{"issue":"8060","key":"3964_CR28","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1038\/s41586-025-08633-8","volume":"640","author":"TE Miller","year":"2025","unstructured":"Miller TE, El Farran CA, Couturier CP, Chen Z, D\u2019Antonio JP, Verga J, et al. Programs, origins and immunomodulatory functions of myeloid cells in glioma. Nature. 2025;640(8060):1072\u201382.","journal-title":"Nature"},{"issue":"13","key":"3964_CR29","doi-asserted-by":"publisher","first-page":"e117","DOI":"10.1093\/nar\/gkw430","volume":"44","author":"Z Ji","year":"2016","unstructured":"Ji Z, Ji H. TSCAN: pseudo-time reconstruction and evaluation in single-cell RNA-seq analysis. Nucleic Acids Res. 2016;44(13):e117.","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"3964_CR30","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1016\/j.cell.2022.04.038","volume":"185","author":"FS Varn","year":"2022","unstructured":"Varn FS, Johnson KC, Martinek J, Huse JT, Nasrallah MP, Wesseling P, et al. Glioma progression is shaped by genetic evolution and microenvironment interactions. Cell. 2022;185(12):2184-99 e16.","journal-title":"Cell"},{"issue":"6389","key":"3964_CR31","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1126\/science.aaf2666","volume":"360","author":"RB Puchalski","year":"2018","unstructured":"Puchalski RB, Shah N, Miller J, Dalley R, Nomura SR, Yoon JG, et al. An anatomic transcriptional atlas of human glioblastoma. Science. 2018;360(6389):660\u20133.","journal-title":"Science"},{"key":"3964_CR32","doi-asserted-by":"publisher","first-page":"495","DOI":"10.3389\/fimmu.2013.00495","volume":"4","author":"L Jardine","year":"2013","unstructured":"Jardine L, Barge D, Ames-Draycott A, Pagan S, Cookson S, Spickett G, et al. Rapid detection of dendritic cell and monocyte disorders using CD4 as a lineage marker of the human peripheral blood antigen-presenting cell compartment. Front Immunol. 2013;4:495.","journal-title":"Front Immunol"},{"issue":"6","key":"3964_CR33","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/j.cell.2019.01.031","volume":"176","author":"P van Galen","year":"2019","unstructured":"van Galen P, Hovestadt V, Wadsworth Ii MH, Hughes TK, Griffin GK, Battaglia S, et al. Single-Cell rna-seq reveals AML hierarchies relevant to disease progression and immunity. Cell. 2019;176(6):1265-81 e24.","journal-title":"Cell"},{"issue":"6","key":"3964_CR34","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1016\/j.cell.2020.02.042","volume":"180","author":"S Devalaraja","year":"2020","unstructured":"Devalaraja S, To TKJ, Folkert IW, Natesan R, Alam MZ, Li M, et al. Tumor-derived retinoic acid regulates intratumoral monocyte differentiation to promote immune suppression. Cell. 2020;180(6):1098-114 e16.","journal-title":"Cell"},{"issue":"1","key":"3964_CR35","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1182\/blood-2009-12-258186","volume":"117","author":"L Sanchez-Martin","year":"2011","unstructured":"Sanchez-Martin L, Estecha A, Samaniego R, Sanchez-Ramon S, Vega MA, Sanchez-Mateos P. The chemokine CXCL12 regulates monocyte-macrophage differentiation and RUNX3 expression. Blood. 2011;117(1):88\u201397.","journal-title":"Blood"},{"key":"3964_CR36","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.biochi.2016.05.002","volume":"127","author":"J Xie","year":"2016","unstructured":"Xie J, Wu X, Zhou Q, Yang Y, Tian Y, Huang C, et al. PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization. Biochimie. 2016;127:121\u201332.","journal-title":"Biochimie"},{"issue":"4","key":"3964_CR37","doi-asserted-by":"publisher","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","volume":"1","author":"A Oeckinghaus","year":"2009","unstructured":"Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009;1(4):a000034.","journal-title":"Cold Spring Harb Perspect Biol"},{"issue":"1","key":"3964_CR38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/cr.2010.177","volume":"21","author":"SC Sun","year":"2011","unstructured":"Sun SC. Non-canonical NF-kappaB signaling pathway. Cell Res. 2011;21(1):71\u201385.","journal-title":"Cell Res"},{"issue":"1","key":"3964_CR39","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s12929-014-0110-2","volume":"22","author":"CY Ko","year":"2015","unstructured":"Ko CY, Chang WC, Wang JM. Biological roles of CCAAT\/Enhancer-binding protein delta during inflammation. J Biomed Sci. 2015;22(1):6.","journal-title":"J Biomed Sci"},{"issue":"6","key":"3964_CR40","doi-asserted-by":"publisher","first-page":"470","DOI":"10.3109\/08830185.2014.902453","volume":"33","author":"K Anbazhagan","year":"2014","unstructured":"Anbazhagan K, Duroux-Richard I, Jorgensen C, Apparailly F. Transcriptomic network support distinct roles of classical and non-classical monocytes in human. Int Rev Immunol. 2014;33(6):470\u201389.","journal-title":"Int Rev Immunol"},{"issue":"8","key":"3964_CR41","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1038\/ni.2063","volume":"12","author":"RN Hanna","year":"2011","unstructured":"Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM, Punt JA, et al. The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat Immunol. 2011;12(8):778\u201385.","journal-title":"Nat Immunol"},{"issue":"1","key":"3964_CR42","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41413-025-00467-4","volume":"13","author":"P Lou","year":"2025","unstructured":"Lou P, Lu X, Li M, Yao Y, Shao X, Shou D, et al. Single-cell sequencing reveals a senescent immune landscape in bone marrow lesions inducing articular cartilage damage in osteoarthritis. Bone Res. 2025;13(1):94.","journal-title":"Bone Res"},{"issue":"1","key":"3964_CR43","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40364-025-00733-x","volume":"13","author":"X Wang","year":"2025","unstructured":"Wang X, Hong Y, Zou J, Zhu B, Jiang C, Lu L, et al. The role of BATF in immune cell differentiation and autoimmune diseases. Biomark Res. 2025;13(1):22.","journal-title":"Biomark Res"},{"key":"3964_CR44","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.semcdb.2024.03.002","volume":"161\u2013162","author":"YF Yazicioglu","year":"2024","unstructured":"Yazicioglu YF, Mitchell RJ, Clarke AJ. Mitochondrial control of lymphocyte homeostasis. Semin Cell Dev Biol. 2024;161\u2013162:42\u201353.","journal-title":"Semin Cell Dev Biol"},{"issue":"12","key":"3964_CR45","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/nmeth.4077","volume":"13","author":"D Turei","year":"2016","unstructured":"Turei D, Korcsmaros T, Saez-Rodriguez J. OmniPath: guidelines and gateway for literature-curated signaling pathway resources. Nat Methods. 2016;13(12):966\u20137.","journal-title":"Nat Methods"},{"issue":"1","key":"3964_CR46","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/jlb.67.1.97","volume":"67","author":"C Buechler","year":"2000","unstructured":"Buechler C, Ritter M, Orso E, Langmann T, Klucken J, Schmitz G. Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. J Leukoc Biol. 2000;67(1):97\u2013103.","journal-title":"J Leukoc Biol"},{"key":"3964_CR47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bbi.2012.11.006","volume":"32","author":"VA Peters","year":"2013","unstructured":"Peters VA, Joesting JJ, Freund GG. IL-1 receptor 2 (IL-1R2) and its role in immune regulation. Brain Behav Immun. 2013;32:1\u20138.","journal-title":"Brain Behav Immun"},{"issue":"7948","key":"3964_CR48","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/s41586-022-05680-3","volume":"614","author":"E Karimi","year":"2023","unstructured":"Karimi E, Yu MW, Maritan SM, Perus LJM, Rezanejad M, Sorin M, et al. Single-cell spatial immune landscapes of primary and metastatic brain tumours. Nature. 2023;614(7948):555\u201363.","journal-title":"Nature"},{"key":"3964_CR49","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.neulet.2017.02.076","volume":"645","author":"L Lisi","year":"2017","unstructured":"Lisi L, Ciotti GM, Braun D, Kalinin S, Curro D, Dello Russo C, et al. Expression of iNOS, CD163 and ARG-1 taken as M1 and M2 markers of microglial polarization in human glioblastoma and the surrounding normal parenchyma. Neurosci Lett. 2017;645:106\u201312.","journal-title":"Neurosci Lett"},{"issue":"7","key":"3964_CR50","doi-asserted-by":"publisher","first-page":"1601478","DOI":"10.1080\/2162402X.2019.1601478","volume":"8","author":"S Liu","year":"2019","unstructured":"Liu S, Zhang C, Maimela NR, Yang L, Zhang Z, Ping Y, et al. Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma. Oncoimmunology. 2019;8(7):1601478.","journal-title":"Oncoimmunology"},{"issue":"1","key":"3964_CR51","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.ccell.2025.11.006","volume":"44","author":"H Piyadasa","year":"2026","unstructured":"Piyadasa H, Oberlton B, Ribi M, Leow K, Ranek JS, Averbukh I, et al. Multi-omic landscape of human gliomas from diagnosis to treatment and recurrence. Cancer Cell. 2026;44(1):112-28 e6.","journal-title":"Cancer Cell"},{"issue":"3","key":"3964_CR52","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/jpm10030112","volume":"10","author":"H Rahimi Koshkaki","year":"2020","unstructured":"Rahimi Koshkaki H, Minasi S, Ugolini A, Trevisi G, Napoletano C, Zizzari IG, et al. Immunohistochemical characterization of immune infiltrate in tumor microenvironment of glioblastoma. J Pers Med. 2020;10(3):112.","journal-title":"J Pers Med"},{"issue":"14","key":"3964_CR53","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1182\/bloodadvances.2017006858","volume":"1","author":"E Ribechini","year":"2017","unstructured":"Ribechini E, Hutchinson JA, Hergovits S, Heuer M, Lucas J, Schleicher U, et al. Novel GM-CSF signals via IFN-gammaR\/IRF-1 and AKT\/mTOR license monocytes for suppressor function. Blood Adv. 2017;1(14):947\u201360.","journal-title":"Blood Adv"},{"issue":"5","key":"3964_CR54","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.immuni.2021.04.004","volume":"54","author":"S Hegde","year":"2021","unstructured":"Hegde S, Leader AM, Merad M. MDSC: Markers, development, states, and unaddressed complexity. Immunity. 2021;54(5):875\u201384.","journal-title":"Immunity"},{"issue":"1","key":"3964_CR55","doi-asserted-by":"publisher","first-page":"1666","DOI":"10.1038\/s41467-024-46148-4","volume":"15","author":"K Miyake","year":"2024","unstructured":"Miyake K, Ito J, Takahashi K, Nakabayashi J, Brombacher F, Shichino S, et al. Single-cell transcriptomics identifies the differentiation trajectory from inflammatory monocytes to pro-resolving macrophages in a mouse skin allergy model. Nat Commun. 2024;15(1):1666.","journal-title":"Nat Commun"},{"issue":"5940","key":"3964_CR56","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1126\/science.1175202","volume":"325","author":"FK Swirski","year":"2009","unstructured":"Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science. 2009;325(5940):612\u20136.","journal-title":"Science"},{"issue":"9","key":"3964_CR57","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1016\/j.celrep.2016.10.052","volume":"17","author":"RL Bowman","year":"2016","unstructured":"Bowman RL, Klemm F, Akkari L, Pyonteck SM, Sevenich L, Quail DF, et al. Macrophage ontogeny underlies differences in tumor-specific education in brain malignancies. Cell Rep. 2016;17(9):2445\u201359.","journal-title":"Cell Rep"},{"issue":"9","key":"3964_CR58","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1158\/0008-5472.CAN-16-2310","volume":"77","author":"Z Chen","year":"2017","unstructured":"Chen Z, Feng X, Herting CJ, Garcia VA, Nie K, Pong WW, et al. Cellular and molecular identity of tumor-associated macrophages in glioblastoma. Cancer Res. 2017;77(9):2266\u201378.","journal-title":"Cancer Res"},{"issue":"1","key":"3964_CR59","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cell.2023.11.032","volume":"187","author":"D Kirschenbaum","year":"2024","unstructured":"Kirschenbaum D, Xie K, Ingelfinger F, Katzenelenbogen Y, Abadie K, Look T, et al. Time-resolved single-cell transcriptomics defines immune trajectories in glioblastoma. Cell. 2024;187(1):149-65 e23.","journal-title":"Cell"},{"issue":"1","key":"3964_CR60","doi-asserted-by":"publisher","first-page":"e12883","DOI":"10.1111\/sji.12883","volume":"92","author":"A Ozanska","year":"2020","unstructured":"Ozanska A, Szymczak D, Rybka J. Pattern of human monocyte subpopulations in health and disease. Scand J Immunol. 2020;92(1):e12883.","journal-title":"Scand J Immunol"},{"issue":"1","key":"3964_CR61","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s13073-023-01205-3","volume":"15","author":"DW Sirkis","year":"2023","unstructured":"Sirkis DW, Warly Solsberg C, Johnson TP, Bonham LW, Sturm VE, Lee SE, et al. Single-cell RNA-seq reveals alterations in peripheral CX3CR1 and nonclassical monocytes in familial tauopathy. Genome Med. 2023;15(1):53.","journal-title":"Genome Med"},{"issue":"1","key":"3964_CR62","doi-asserted-by":"publisher","first-page":"fcaa013","DOI":"10.1093\/braincomms\/fcaa013","volume":"2","author":"RB McGill","year":"2020","unstructured":"McGill RB, Steyn FJ, Ngo ST, Thorpe KA, Heggie S, Ruitenberg MJ, et al. Monocytes and neutrophils are associated with clinical features in amyotrophic lateral sclerosis. Brain Commun. 2020;2(1):fcaa013.","journal-title":"Brain Commun"},{"issue":"5","key":"3964_CR63","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s00401-014-1345-4","volume":"128","author":"V Grozdanov","year":"2014","unstructured":"Grozdanov V, Bliederhaeuser C, Ruf WP, Roth V, Fundel-Clemens K, Zondler L, et al. Inflammatory dysregulation of blood monocytes in Parkinson\u2019s disease patients. Acta Neuropathol. 2014;128(5):651\u201363.","journal-title":"Acta Neuropathol"},{"issue":"7","key":"3964_CR64","doi-asserted-by":"publisher","first-page":"1626","DOI":"10.1016\/j.cell.2020.04.055","volume":"181","author":"E Friebel","year":"2020","unstructured":"Friebel E, Kapolou K, Unger S, Nunez NG, Utz S, Rushing EJ, et al. Single-cell mapping of human brain cancer reveals tumor-specific instruction of tissue-invading leukocytes. Cell. 2020;181(7):1626-42 e20.","journal-title":"Cell"},{"issue":"4","key":"3964_CR65","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1038\/s41593-020-00789-y","volume":"24","author":"AR Pombo Antunes","year":"2021","unstructured":"Pombo Antunes AR, Scheyltjens I, Lodi F, Messiaen J, Antoranz A, Duerinck J, et al. Single-cell profiling of myeloid cells in glioblastoma across species and disease stage reveals macrophage competition and specialization. Nat Neurosci. 2021;24(4):595\u2013610.","journal-title":"Nat Neurosci"},{"issue":"1","key":"3964_CR66","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1038\/s41467-023-37361-8","volume":"14","author":"Z Chen","year":"2023","unstructured":"Chen Z, Soni N, Pinero G, Giotti B, Eddins DJ, Lindblad KE, et al. Monocyte depletion enhances neutrophil influx and proneural to mesenchymal transition in glioblastoma. Nat Commun. 2023;14(1):1839.","journal-title":"Nat Commun"},{"key":"3964_CR67","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1146\/annurev-immunol-101819-082015","volume":"39","author":"EM Steinert","year":"2021","unstructured":"Steinert EM, Vasan K, Chandel NS. Mitochondrial metabolism regulation of T cell-mediated immunity. Annu Rev Immunol. 2021;39:395\u2013416.","journal-title":"Annu Rev Immunol"},{"key":"3964_CR68","doi-asserted-by":"publisher","first-page":"e52330","DOI":"10.7554\/eLife.52330","volume":"9","author":"A Kumar","year":"2020","unstructured":"Kumar A, Chamoto K, Chowdhury PS, Honjo T. Tumors attenuating the mitochondrial activity in T cells escape from PD-1 blockade therapy. Elife. 2020;9:e52330.","journal-title":"Elife"},{"issue":"1","key":"3964_CR69","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/cmi.2016.34","volume":"14","author":"D Bertheloot","year":"2017","unstructured":"Bertheloot D, Latz E. HMGB1, IL-1alpha, IL-33 and S100 proteins: dual-function alarmins. Cell Mol Immunol. 2017;14(1):43\u201364.","journal-title":"Cell Mol Immunol"},{"issue":"1","key":"3964_CR70","doi-asserted-by":"publisher","first-page":"vdad035","DOI":"10.1093\/noajnl\/vdad035","volume":"5","author":"SJ Lorrey","year":"2023","unstructured":"Lorrey SJ, Waibl Polania J, Wachsmuth LP, Hoyt-Miggelbrink A, Tritz ZP, Edwards R, et al. Systemic immune derangements are shared across various CNS pathologies and reflect novel mechanisms of immune privilege. Neuro-Oncol Adv. 2023;5(1):vdad035.","journal-title":"Neuro-Oncol Adv"},{"issue":"1","key":"3964_CR71","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/s41467-023-35957-8","volume":"14","author":"S Zhou","year":"2023","unstructured":"Zhou S, Huang Y, Chen Y, Liu Y, Xie L, You Y, et al. Reprogramming systemic and local immune function to empower immunotherapy against glioblastoma. Nat Commun. 2023;14(1):435.","journal-title":"Nat Commun"},{"issue":"1","key":"3964_CR72","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13046-025-03359-x","volume":"44","author":"D Bhatia","year":"2025","unstructured":"Bhatia D, Dolcetti R, Mazzieri R. Are monocytes a preferable option to develop myeloid cell-based therapies for solid tumors? J Exp Clin Cancer Res. 2025;44(1):98.","journal-title":"J Exp Clin Cancer Res"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-026-03964-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03964-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03964-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:02:12Z","timestamp":1788955332000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12974-026-03964-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3964"],"URL":"https:\/\/doi.org\/10.1186\/s12974-026-03964-3","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"assertion":[{"value":"7 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The collection of blood and tumor tissue from glioblastoma patients is a procedure routinely carried out in the framework of a collaboration between the Neurosurgery Centre at the Centre Hospitalier de Luxembourg (CHL) and the NORLUX Neuro-Oncology Laboratory at the Luxembourg Institute of Health (LIH) (\n                      \n                      ). All patients received a detailed information sheet and signed an informed consent form to agree to provide blood and tissue for research. The procedure was approved by the National Ethics Committee for Research (CNER, PRECISION-PDX, AVIS 201201\/06), and the data collection including clinical and genetic data was authorized under pseudo-anonymized format and supervised by the National Data Protection Committee (CNPD, 929\/2017) in Luxembourg. The CNER also approved the collection of blood samples from healthy donors (HEALTHY BLOOD, AVIS 202202\/02).","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Priority patent application filed on predictive and diagnostic biomarkers for glioma\/glioblastoma (patent applicant: Luxembourg Institute of Health; inventors: AM, AnS, AP and BM). All other authors declare that they have no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"306"}}