{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:57:12Z","timestamp":1785412632575,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,20]]},"group-title":"Immunology","reference-count":67,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"Center for Cancer Research, National Cancer Institute, National Institutes of Health Intramural Research Program","award":["ZIA BC 011877"],"award-info":[{"award-number":["ZIA BC 011877"]}]},{"name":"National Cancer Institute, National Institutes of Health","award":["HHSN261200800001E."],"award-info":[{"award-number":["HHSN261200800001E."]}]},{"name":"Ludwig Institute for Cancer Research"},{"id":[{"id":"https:\/\/ror.org\/04q062s21","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"crossref","award":["P300P3_155374"],"award-info":[{"award-number":["P300P3_155374"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academy of Medical Sciences Springboard Award","award":["SBF0011\\1077"],"award-info":[{"award-number":["SBF0011\\1077"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1R35NS142982"],"award-info":[{"award-number":["1R35NS142982"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Glioblastoma is a lethal brain tumor that is unresponsive to current cancer immunotherapeutic approaches, including immune checkpoint blockade (ICB). This suggests that initial priming of T cells, rather than their expansion and licensing as effectors, is a restricting feature in this tumor setting. To overcome the limited initiation of CD8\n                  <jats:sup>+<\/jats:sup>\n                  T cell responses, we employed a strong heterologous prime-boost vaccination with the simian adenovirus ChAdOx1 and poxvirus modified vaccinia Ankara (MVA). Vaccination conferred therapeutic efficacy against orthotopic, immune checkpoint-blockade (ICB)-refractory SB28 murine glioblastoma. Vaccination was effective against both the murine tumor antigen, P1A, and a newly identified glioblastoma-associated antigen, Gpr149. Additional treatment with ICB provided no additional benefit. Systemic ChAdOx1\/MVA vaccination induced robust infiltration of antigen-specific T cells in tumor-challenged brains, the majority of which exhibited a CD103\n                  <jats:sup>+<\/jats:sup>\n                  CD69\n                  <jats:sup>+<\/jats:sup>\n                  CD8\n                  <jats:sup>+<\/jats:sup>\n                  tissue-resident memory (TRM)-like phenotype. These cells were polyfunctional, durable in brains with sustained tumor control, and mediated tissue-specific immunological memory. Moreover, intracranial adoptive transfer of glioblastoma-derived antigen-specific TRM-like cells was sufficient to protect na\u00efve recipients from subsequent orthotopic tumor challenge. Together, these findings establish that viral vector vaccination can generate tumor-specific TRM-like cells that mediate effective anti-glioblastoma immunity, providing a rationale for clinical evaluation of ChAdOx1\/MVA-based strategies in glioblastoma.\n                <\/jats:p>","DOI":"10.64898\/2026.06.18.733241","type":"posted-content","created":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T11:10:14Z","timestamp":1782040214000},"source":"Crossref","is-referenced-by-count":0,"title":["Systemic viral vector vaccination induces brain resident memory T cells to drive anti-glioblastoma immunity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3350-9818","authenticated-orcid":false,"given":"Emily E.","family":"Steffke","sequence":"first","affiliation":[{"name":"Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA"},{"name":"Ludwig Institute for Cancer 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