{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:28:42Z","timestamp":1792114122368,"version":"4.4.0"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T00:00:00Z","timestamp":1669161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lieselotte Beutel Stiftung","award":["03Z22DN11"],"award-info":[{"award-number":["03Z22DN11"]}]},{"name":"Lieselotte Beutel Stiftung","award":["03Z22Di1"],"award-info":[{"award-number":["03Z22Di1"]}]},{"name":"Comprehensive Cancer Center Mecklenburg-Vorpommern","award":["03Z22DN11"],"award-info":[{"award-number":["03Z22DN11"]}]},{"name":"Comprehensive Cancer Center Mecklenburg-Vorpommern","award":["03Z22Di1"],"award-info":[{"award-number":["03Z22Di1"]}]},{"name":"Forschungsverbund Molekulare Medizin","award":["03Z22DN11"],"award-info":[{"award-number":["03Z22DN11"]}]},{"name":"Forschungsverbund Molekulare Medizin","award":["03Z22Di1"],"award-info":[{"award-number":["03Z22Di1"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["03Z22DN11"],"award-info":[{"award-number":["03Z22DN11"]}]},{"name":"Deutsche Forschungsgemeinschaft","award":["03Z22Di1"],"award-info":[{"award-number":["03Z22Di1"]}]},{"name":"German Federal Ministry of Education and Research","award":["03Z22DN11"],"award-info":[{"award-number":["03Z22DN11"]}]},{"name":"German Federal Ministry of Education and Research","award":["03Z22Di1"],"award-info":[{"award-number":["03Z22Di1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Glioblastoma is the most common and lethal primary brain malignancy that almost inevitably recurs as therapy-refractory cancer. While the success of immune checkpoint blockade (ICB) revealed the immense potential of immune-targeted therapies in several types of cancers outside the central nervous system, it failed to show objective responses in glioblastoma patients as of now. The ability of glioblastoma cells to drive multiple modes of T cell dysfunction while exhibiting low-quality neoepitopes, low-mutational load, and poor antigen priming limits anti-tumor immunity and efficacy of antigen-unspecific immunotherapies such as ICB. An in-depth understanding of the GBM immune landscape is essential to delineate and reprogram such immunosuppressive circuits during disease progression. In this view, the present study aimed to characterize the peripheral and intratumoral immune compartments of 35 glioblastoma patients compared to age- and sex-matched healthy control probands, particularly focusing on exhaustion signatures on myeloid and T cell subsets. Compared to healthy control participants, different immune signatures were already found in the peripheral circulation, partially related to the steroid medication the patients received. Intratumoral CD4+ and CD8+ TEM cells (CD62Llow\/CD45ROhigh) revealed a high expression of PD1, which was also increased on intratumoral, pro-tumorigenic macrophages\/microglia. Histopathological analysis further identified high PSGL-1 expression levels of the latter, which has recently been linked to increased metastasis in melanoma and colon cancer via P-selectin-mediated platelet activation. Overall, the present study comprises immunophenotyping of a patient cohort to give implications for eligible immunotherapeutic targets in neurooncology in the future.<\/jats:p>","DOI":"10.3390\/cancers14235751","type":"journal-article","created":{"date-parts":[[2022,11,23]],"date-time":"2022-11-23T03:15:24Z","timestamp":1669173324000},"page":"5751","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Immunophenotyping of Circulating and Intratumoral Myeloid and T Cells in Glioblastoma Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Sascha","family":"Marx","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA"},{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Wilken","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"},{"name":"ZIK <i>plasmatis<\/i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7411-9299","authenticated-orcid":false,"given":"Lea","family":"Miebach","sequence":"additional","affiliation":[{"name":"ZIK <i>plasmatis<\/i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany"},{"name":"Department for General, Thoracic, Vascular, and Thorax Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Ispirjan","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02215, USA"},{"name":"ZIK <i>plasmatis<\/i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik","family":"Kinnen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"},{"name":"Department of Pharmacology, C_DAT, Greifswald University Medical Center, Felix-Hausdorff-Str. 3, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0603-8953","authenticated-orcid":false,"given":"Sandra","family":"Bien-M\u00f6ller","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"},{"name":"Department of Pharmacology, C_DAT, Greifswald University Medical Center, Felix-Hausdorff-Str. 3, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2950-0984","authenticated-orcid":false,"given":"Eric","family":"Freund","sequence":"additional","affiliation":[{"name":"ZIK <i>plasmatis<\/i>, Leibniz Institute for Plasma Science and Technology (INP), Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany"},{"name":"Department for General, Thoracic, Vascular, and Thorax Surgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Baldauf","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Fleck","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Siebert","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Greifswald University Medical Center, Ferdinand-Sauerbruch-Str., 17475 Greifswald, 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