{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:34:14Z","timestamp":1790289254209,"version":"4.1.0"},"reference-count":124,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Oncolytic viruses (OVs) represent a unique therapeutic platform that combines tumor-selective replication with potent immunomodulatory capacity. In addition to direct oncolysis, OVs can convert tumors into inflammatory niches that support antigen release, dendritic cell activation, and cytotoxic T lymphocyte priming. However, durable responses remain inconsistent across tumor types and patient populations, largely due to tumor immune tolerance mechanisms that restrict both viral propagation and the development of effective anti-tumor immunity. Toll-like receptors (TLRs), as key pattern recognition receptors, play central roles in sensing viral nucleic acids and infection-associated danger signals, orchestrating type I interferon responses, NF-\u03baB-driven inflammation, and downstream adaptive immunity. Notably, TLR signaling is a double-edged sword in virotherapy: it can promote antigen presentation and immune activation while simultaneously accelerating antiviral clearance and limiting intratumoral viral spread. Chemotherapy, a mainstay of cancer treatment, further shapes OV efficacy by altering lymphocyte availability, antigen presentation, myeloid composition, and the balance between immunogenic cell death and immunosuppression. Emerging evidence supports that rational OV-chemotherapy combinations can synergize by enhancing tumor antigen release, reprogramming suppressive myeloid compartments, and creating temporal windows for immune checkpoint blockade. In this review, we summarize the mechanisms underlying tumor immune tolerance, discuss how TLR-mediated innate sensing shapes OV-induced anti-tumor immunity, and evaluate how chemotherapy modulates these interactions. We propose mechanistic frameworks and translational considerations including scheduling, biomarkers, and immune monitoring to guide the development of next-generation OV combination strategies in chemotherapy-treated cancer patients.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1898807","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T11:36:08Z","timestamp":1785497768000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The interplay between oncolytic viruses, Toll-like receptor signaling, and chemotherapy in overcoming tumor immune tolerance"],"prefix":"10.3389","volume":"16","author":[{"given":"Yi-Ying","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"The iEGG and Animal Biotechnology Center, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Hsu","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of General Surgery, Department of Surgery, Taichung Veterans General Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Critical Care, Taichung Veterans General Hospital","place":["Taichung, Taiwan"]},{"name":"Department of Nursing, Hung Kuang University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yuan","family":"Tseng","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pin-Kuan","family":"Chiang","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Muniri","sequence":"additional","affiliation":[{"name":"Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University","place":["Lancaster, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Jen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"The iEGG and Animal Biotechnology Center, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Rong Hsing Research Center for Translational Medicine, National Chung Hsing University","place":["Taichung, Taiwan"]},{"name":"Department of Life Sciences, National Chung Hsing University","place":["Taichung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"574","DOI":"10.18502\/ijm.v14i4.10245","article-title":"Development of gold nanoparticles-lateral flow test as a novel field diagnostic assay for detecting foot-and-mouth disease and lumpy skin disease viruses","volume":"14","author":"Abdalhamed","year":"2022","journal-title":"Iran. 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