{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:12:33Z","timestamp":1788487953827,"version":"build-2803163510"},"reference-count":30,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"unspecified","delay-in-days":29,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R21 NS083171"],"award-info":[{"award-number":["R21 NS083171"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R35 NS105068"],"award-info":[{"award-number":["R35 NS105068"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003156","name":"Musella Foundation For Brain Tumor Research and Information","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA047904"],"award-info":[{"award-number":["P30 CA047904"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA222965"],"award-info":[{"award-number":["R01 CA222965"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,5,16]]},"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>While adoptive transfer of T-cells has been a major medical breakthrough for patients with B cell malignancies, the development of safe and effective T-cell-based immunotherapy for central nervous system (CNS) tumors, such as glioblastoma (GBM), still needs to overcome multiple challenges, including effective homing and persistence of T-cells. Based on previous observations that interleukin (IL)-17-producing T-cells can traffic to the CNS in autoimmune conditions, we evaluated CD8<jats:sup>+<\/jats:sup> T-cells that produce IL-17 and interferon-\u03b3 (IFN-\u03b3) (Tc17-1) cells in a preclinical GBM model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We differentiated Pmel-1 CD8<jats:sup>+<\/jats:sup> T-cells into Tc17-1 cells and compared their phenotypic and functional characteristics with those of IFN-\u03b3-producing CD8<jats:sup>+<\/jats:sup> T (Tc1) and IL-17-producing CD8<jats:sup>+<\/jats:sup> T (Tc17) cells. We also evaluated the therapeutic efficacy, persistence, and tumor-homing of Tc17-1 cells in comparison to Tc1 cells using a mouse GL261 glioma model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In vitro, Tc17-1 cells demonstrated profiles of both Tc1 and Tc17 cells, including production of both IFN-\u03b3 and IL-17, although Tc17-1 cells demonstrated lesser degrees of antigen-specific cytotoxic activity compared with Tc1 cells. In mice-bearing intracranial GL261-Quad tumor and treated with temozolomide, Tc1 cells, but not Tc17-1, showed a significant prolongation of survival. However, when the T-cell transfer was combined with poly-ICLC and Pmel-1 peptide vaccine, both Tc1 and Tc17-1 cells exhibited significantly prolonged survival associated with upregulation of very late activation antigen\u22124 on Tc17-1 cells in vivo. Glioma cells that recurred following the therapy lost the susceptibility to Pmel-1-derived cytotoxic T-cells, indicating that immuno-editing was a mechanism of the acquired resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Tc17-1 cells were equally effective as Tc1 cells when combined with poly-ICLC and peptide vaccine treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-002426","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T12:18:25Z","timestamp":1625055505000},"page":"e002426","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":18,"title":["IFN-\u03b3- and IL-17-producing CD8<sup>+<\/sup> T (Tc17-1) cells in combination with poly-ICLC and peptide vaccine exhibit antiglioma activity"],"prefix":"10.1136","volume":"9","author":[{"given":"Takayuki","family":"Ohkuri","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Brain Tumor Program, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akemi","family":"Kosaka","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Brain Tumor Program, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Ikeura","sequence":"additional","affiliation":[{"name":"Brain Tumor Program, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres M","family":"Salazar","sequence":"additional","affiliation":[{"name":"Oncovir, Inc, Washington, District of Columbia, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0076-9920","authenticated-orcid":false,"given":"Hideho","family":"Okada","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA"},{"name":"Brain Tumor Program, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, Pittsburgh, PA, USA"},{"name":"Department of Neurological Surgery, University of California San Francisco, San Francisco, California, USA"},{"name":"Parker Institute for Cancer Immunotherapy, San Francisco, CA, 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