{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:39:24Z","timestamp":1792600764000,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":278,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA076292"],"award-info":[{"award-number":["P30 CA076292"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Quantitative Imaging Core","award":["R01 NS131912"],"award-info":[{"award-number":["R01 NS131912"]}]},{"name":"Moffitt Cancer Center Team Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The tumor microenvironment (TME) is a critical determinant of glioma response to therapies, including immunotherapy. We have classified the immune TME of gliomas by multiplex immunofluorescence (mIF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tissue taken at initial resection from 354 patients with newly diagnosed glioma grades 2-4 were analyzed using 3 mIF panels of markers for T, B, and myeloid cells. Tumor cores were characterized by the relative abundances of: (i) 15 primary immune phenotypes, (ii) 96 secondary immune phenotypes, and (iii) 29 biologically meaningful multi-marker immune phenotypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Unsupervised cluster analysis of WHO grade 4 diffuse gliomas revealed four subtypes \u03b1, \u03b2, \u03b3, and \u03b4 that were internally reproducible. Immune subtype \u03b1 was characterized by high abundance of antigen-presenting cells (APCs) and low levels of MHC II\u2212 monocytes. Subtype \u03b2 was high in regulatory T cells and myeloid cells, but low in lymphocytes with effector functions. Subtype \u03b3 displayed high abundance of immune cell phenotypes, particularly lymphocytes with effector or helper functions. Subtype \u03b4 was low in immune phenotypes, with poorer outcomes. Grade 3 tumors could also be classified into \u03b1, \u03b2, \u03b3, and \u03b4 subtypes, indicating generalizability of these immune TME subtypes across high-grade gliomas. Additionally, grade 2 tumors could be classified into subtypes \u03b5, \u03c1 and \u03c4 identified in grade 3 tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We have identified internally reproducible criteria for classifying gliomas according to the immune microenvironment, findings that could aid our understanding of the natural progression of low- and high-grade gliomas and inform the rational application of immune-oncologic therapeutic interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/noajnl\/vdag257","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T11:46:13Z","timestamp":1790941573000},"source":"Crossref","is-referenced-by-count":0,"title":["Immune subtypes and survival in patients with primary 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