{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:02:19Z","timestamp":1777953739050,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,30]]},"group-title":"Oncology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Gliomas are heterogeneous tumors with poor outcomes following current therapies, including immunotherapy. The tumor microenvironment (TME) is a critical determinant of therapeutic response in gliomas. 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\u2212diagnosed glioma grades 2-4 were analyzed using three 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>Using unsupervised cluster analysis of WHO grade 4 gliomas we identified 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 lymphoid and myeloid immune phenotypes and APCs, 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.<\/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":"10.64898\/2026.04.29.26351981","type":"posted-content","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:10:11Z","timestamp":1777590611000},"source":"Crossref","is-referenced-by-count":0,"title":["Immune Subtypes and Survival in Patients with Primary Glioma"],"prefix":"10.64898","author":[{"given":"Yu","family":"Fang","sequence":"first","affiliation":[{"name":"Dept. of Mathematics & Statistics, University of South Florida, Tampa, FL, USA"},{"name":"Dept. of Metabolism & Physiology, Moffitt Cancer Center, Tampa, FL 33612, USA"},{"name":"Dept. of Radiology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiwoong","family":"Kim","sequence":"additional","affiliation":[{"name":"Dept. of Mathematics & Statistics, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Dept. of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngchul","family":"Kim","sequence":"additional","affiliation":[{"name":"Dept. of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harshan","family":"Ravi","sequence":"additional","affiliation":[{"name":"Dept. of Metabolism & Physiology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asim","family":"Mazin","sequence":"additional","affiliation":[{"name":"Dept. of Metabolism & Physiology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos M.","family":"Moran\u2212Segura","sequence":"additional","affiliation":[{"name":"Advanced Analytical and Digital Laboratory, Moffitt Cancer Center, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Advanced Analytical and Digital Laboratory, Moffitt Cancer Center, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Macaulay","sequence":"additional","affiliation":[{"name":"Dept. of Anatomic Pathology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Veglia","sequence":"additional","affiliation":[{"name":"Genome Regulation and Cell Signaling Program, The Wistar Institute, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reid C.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Dept. of Neurological Surgery, Vanderbilt University Medical Center, Nashville, TN 37212, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sajeel A.","family":"Chowdhary","sequence":"additional","affiliation":[{"name":"Tampa General Hospital Cancer Center, Tampa General Hospital, Tampa, FL 33606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Egan","sequence":"additional","affiliation":[{"name":"Dept. of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8893-7687","authenticated-orcid":false,"given":"Natarajan","family":"Raghunand","sequence":"additional","affiliation":[{"name":"Dept. of Metabolism & Physiology, Moffitt Cancer Center, Tampa, FL 33612, USA"},{"name":"Dept. of Radiology, Moffitt Cancer Center, Tampa, FL 33612, USA"},{"name":"Dept. of Oncologic Sciences, University of South Florida, Tampa, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026050409350718000_2026.04.29.26351981v1.1","doi-asserted-by":"crossref","unstructured":"Karschnia P , Young JS , Youssef GC , et al. 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