{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:59:18Z","timestamp":1788461958268,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2018\/31\/D\/NZ5\/01754"],"award-info":[{"award-number":["2018\/31\/D\/NZ5\/01754"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Brachytherapy (BT) is a local radiation treatment method for solid tumors. A single 10 Gy high\u2013dose\u2013rate (HDR) BT acts as an \u201cin situ\u201d vaccination. Tumor microenvironment (TME)\u2013dependent radio\u2013resistance mechanisms, such as increasing immunosuppression and hypoxia, lead to tumor recurrence after radiotherapy. Our study aimed to determine whether adding imiquimod (IMQ) to anticancer therapy would overcome TME\u2013mediated mechanisms of radiotherapy resistance. IMQ, a toll\u2013like receptor 7 (TLR7) agonist, acts as an immunostimulant and a vascular normalizing agent. Methods: Mice with well\u2013developed tumors were treated with IMQ at a vascular\u2013normalized dose of 50 \u03bcg, followed 5 days later by a single 10 Gy HDR BT. The dose coverage was planned using Discovery RT computed tomography CT scans. Irradiation was performed with a high\u2013dose\u2013rate afterloader equipped with an iridium\u2013192 radioactive source. Results: In mice treated with a combination of IMQ and BT, we observed significant inhibition of melanoma tumor growth. We also noticed an effective therapeutic effect in mice with breast cancer, resulting in significantly prolonged survival and complete tumor regression in 20% of treated mice. In the blood of treated mice, we observed leukopenia with eosinophilia. In tumors, there was enhanced infiltration by cytotoxic CD8+ T lymphocytes. The depletion of CD8+ T cells completely abolished the effect of the combined therapy. Conclusions: The combination of IMQ with HDR brachytherapy induces a synergistic effect, improving the therapeutic antitumor effect of brachytherapy. Our data indicate that it is reasonable to use drugs that prevent changes in the TME in combination with radiotherapy.<\/jats:p>","DOI":"10.3390\/cancers18050745","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T13:58:03Z","timestamp":1772114283000},"page":"745","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TLR7 Agonist Imiquimod Improves the Therapeutic Antitumor Effect of High\u2013Dose\u2013Rate Brachytherapy"],"prefix":"10.3390","volume":"18","author":[{"given":"Magdalena","family":"Jarosz-Biej","sequence":"first","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1131-289X","authenticated-orcid":false,"given":"Ryszard","family":"Smolarczyk","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6203-622X","authenticated-orcid":false,"given":"Dorota","family":"Sprus-Lipka","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Szlag","sequence":"additional","affiliation":[{"name":"Radiotherapy Planning Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Urba\u015b","sequence":"additional","affiliation":[{"name":"Brachytherapy Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Czapla","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5325-2369","authenticated-orcid":false,"given":"Joanna","family":"Ciep\u0142a","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2616-4560","authenticated-orcid":false,"given":"Karolina","family":"Sinek","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-0821","authenticated-orcid":false,"given":"Alina","family":"Drzyzga","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Pilny","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Wojcieszek","sequence":"additional","affiliation":[{"name":"Brachytherapy Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Cicho\u0144","sequence":"additional","affiliation":[{"name":"Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrze\u017ce Armii Krajowej Street 15, 44-101 Gliwice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sminia, P., Guipaud, O., Viktorsson, K., Ahire, V., Baatout, S., Boterberg, T., Cizkova, J., Dost\u00e1l, M., Fernandez-Palomo, C., and Filipova, A. 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