{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:51:19Z","timestamp":1768571479184,"version":"3.49.0"},"posted":{"date-parts":[[2025,4,25]]},"group-title":"Pharmacology and Therapeutics","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,4,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Intratumor (IT) inoculation of the rhino:poliovirus chimera, PVSRIPO, yielded objective radiographic responses with long-term survival in 20% of patients with recurrent glioblastoma (rGBM). PVSRIPO infects dendritic cells (DCs) and sets up non-cytopathogenic viral (v)RNA replication, which triggers sustained type-I IFN (IFN-I) signaling and antitumor T cell priming. Here we identify IFN-I signaling in glioma-draining cervical lymph nodes (cLN) as a mediator of polio virotherapy. Transient IFN-I signaling after IT therapy was rescued by cervical perilymphatic injection (CPLI) of PVSRIPO, targeting cLN directly. Dual-site (IT+CPLI) PVSRIPO induced profound inflammatory reprogramming of cLN, enhanced vRNA replication and IFN-I signaling in DCs and High Endothelial Venules (HEV), augmented anti-glioma efficacy in mice, and was associated with T cell activation in rGBM patients. A Ph2 clinical trial of IT+CPLI PVSRIPO is ongoing (\n                  <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06177964\">NCT06177964<\/jats:ext-link>\n                  ). This work implicates the lymphatic system as a novel virotherapy target and demonstrates the CPLI concept to complement brain tumor immunotherapy.\n                <\/jats:p>","DOI":"10.1101\/2025.04.23.25326279","type":"posted-content","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T21:10:37Z","timestamp":1745615437000},"source":"Crossref","is-referenced-by-count":0,"title":["Lymphotropic Virotherapy Engages DC and High Endothelial Venule Inflammation to Mediate Cancer\n                  <i>In Situ<\/i>\n                  Vaccination"],"prefix":"10.64898","author":[{"given":"Andrea L.","family":"Ludwig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary P.","family":"McKay","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Griffin P.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark 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