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M2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (TME) and bias immunity toward type 2, away from the type 1 mechanisms with antitumor properties. To drive type 1 immunity in CNS tissues, we infected GL261 tumor\u2013bearing mice with attenuated rabies virus (RABV). These neurotropic viruses spread to CNS tissues trans-axonally, where they induce a strong type 1 immune response that involves Th1, CD8, and B cell entry across the blood\u2013brain barrier and virus clearance in the absence of overt sequelae. Intranasal infection with attenuated RABV prolonged the survival of mice bearing established GL261 brain tumors. Despite the failure of virus spread to the tumor, infection resulted in significantly enhanced tumor necrosis, extensive CD4 T cell accumulation, and high levels of the proinflammatory factors IFN-\u03b3, TNF-\u03b1, and inducible NO synthase in the TME merely 4 d postinfection, before significant virus spread or the appearance of RABV-specific immune mechanisms in CNS tissues. Although the majority of infiltrating CD4 cells appeared functionally inactive, the proinflammatory changes in the TME later resulted in the loss of accumulating M2 and increased M1 TAMs. Mice deficient in the Th1 transcription factor T-bet did not gain any survival advantage from RABV infection, exhibiting only limited tumor necrosis and no change in TME cytokines or TAM phenotype and highlighting the importance of type 1 mechanisms in this process.<\/jats:p>","DOI":"10.4049\/jimmunol.1601444","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:30:25Z","timestamp":1493685025000},"page":"4513-4523","source":"Crossref","is-referenced-by-count":11,"title":["Type 1 Immune Mechanisms Driven by the Response to Infection with Attenuated Rabies Virus Result in Changes in the Immune Bias of the Tumor Microenvironment and Necrosis of Mouse GL261 Brain Tumors"],"prefix":"10.1093","volume":"198","author":[{"given":"Emily K","family":"Bongiorno","sequence":"first","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha A","family":"Garcia","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7278-341X","authenticated-orcid":false,"given":"Sami","family":"Sauma","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-5104","authenticated-orcid":false,"given":"D Craig","family":"Hooper","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Thomas Jefferson University , Philadelphia, PA 19107"},{"name":"Department of Neurological Surgery, Thomas Jefferson University , Philadelphia, PA 19107"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,6,1]]},"reference":[{"key":"2025030615164021400_r1","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1586\/erv.13.41","article-title":"An update on vaccine therapy and other immunotherapeutic approaches for glioblastoma","volume":"12","author":"Reardon","year":"2013","journal-title":"Expert Rev. 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