{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T20:11:15Z","timestamp":1784578275639,"version":"3.55.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T00:00:00Z","timestamp":1640908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johannes Gutenberg-Universit\u00e4t Mainz"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human papilloma virus (HPV) infection is a causative agent for several cancers types (genital, anal and head and neck region). The HPV E6 and E7 proteins are oncogenic drivers and thus are ideal candidates for therapeutic vaccination. We recently reported that a novel ribonucleic acid lipoplex (RNA-LPX)-based HPV16 vaccine, E7 RNA-LPX, mediates regression of mouse HPV16<jats:sup>+<\/jats:sup> tumors and establishes protective <jats:italic>T <\/jats:italic>cell memory. An HPV16 E6\/E7 RNA-LPX vaccine is currently being investigated in two phase I and II clinical trials in various HPV-driven cancer types; however, it remains a high unmet medical need for treatments for patients with radiosensitive HPV16<jats:sup>+<\/jats:sup> tumors. Therefore, we set out to investigate the therapeutic efficacy of E7 RNA-LPX vaccine combined with standard-of-care local radiotherapy (LRT). We demonstrate that E7 RNA-LPX synergizes with LRT in HPV16<jats:sup>+<\/jats:sup> mouse tumors, with potent therapeutic effects exceeding those of either monotherapy. Mode of action studies revealed that the E7\u00a0RNA-LPX vaccine induced high numbers of intratumoral-E7-specific CD8<jats:sup>+<\/jats:sup><jats:italic>T <\/jats:italic>cells, rendering cold tumors immunologically hot, whereas LRT primarily acted as a cytotoxic therapy, reducing tumor mass and intratumor hypoxia by predisposing tumor cells to antigen-specific <jats:italic>T <\/jats:italic>cell-mediated killing. Overall, LRT enhanced the effector function of E7 RNA-LPX-primed <jats:italic>T <\/jats:italic>cell responses. The therapeutic synergy was dependent on total radiation dose, rather than radiation dose-fractionation. Together, these results show that LRT synergizes with E7 RNA-LPX and enhances its anti-tumor activity against HPV16<jats:sup>+<\/jats:sup> cancer models. This work paves into a new translational therapy for HPV16<jats:sup>+<\/jats:sup> cancer patients.<\/jats:p>","DOI":"10.1007\/s00262-021-03134-9","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T16:02:57Z","timestamp":1640966577000},"page":"1975-1988","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Local radiotherapy and E7 RNA-LPX vaccination show enhanced therapeutic efficacy in preclinical models of HPV16+ cancer"],"prefix":"10.1007","volume":"71","author":[{"given":"Nadja","family":"Salomon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abderaouf","family":"Selmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Grunwitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Stanganello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Neumaier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jutta","family":"Petschenka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Diken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Kreiter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zlem","family":"T\u00fcreci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ugur","family":"Sahin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9839-3484","authenticated-orcid":false,"given":"Fulvia","family":"Vascotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,31]]},"reference":[{"key":"3134_CR1","unstructured":"Does HPV Genital HPV Infection\u2013CDC Fact Sheet, https:\/\/www.cdc.gov\/std\/hpv\/hpv-Fs-July-2017.pdf"},{"issue":"2","key":"3134_CR2","first-page":"80","volume":"40","author":"P Brianti","year":"2017","unstructured":"Brianti P, de Flammineis E, Mercuri SR (2017) Review of HPV-related diseases and cancers. New Microbiol 40(2):80\u201385","journal-title":"New Microbiol"},{"issue":"4","key":"3134_CR3","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1002\/ijc.30716","volume":"141","author":"C de Martel","year":"2017","unstructured":"de Martel C, Plummer M, Vignat J et al (2017) Worldwide burden of cancer attributable to HPV by site, country and HPV type. Int J Cancer 141(4):664\u2013670. https:\/\/doi.org\/10.1002\/ijc.30716","journal-title":"Int J Cancer"},{"issue":"Suppl 5","key":"3134_CR4","doi-asserted-by":"publisher","first-page":"v184","DOI":"10.1093\/annonc\/mdq185","volume":"21","author":"V Gr\u00e9goire","year":"2010","unstructured":"Gr\u00e9goire V, Lefebvre J-L, Licitra L et al (2010) Squamous cell carcinoma of the head and neck: EHNS-ESMO-ESTRO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21(Suppl 5):v184\u2013v186. https:\/\/doi.org\/10.1093\/annonc\/mdq185","journal-title":"Ann Oncol"},{"issue":"1","key":"3134_CR5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1056\/NEJMoa0912217","volume":"363","author":"KK Ang","year":"2010","unstructured":"Ang KK, Harris J, Wheeler R et al (2010) Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 363(1):24\u201335. https:\/\/doi.org\/10.1056\/NEJMoa0912217","journal-title":"N Engl J Med"},{"issue":"10","key":"3134_CR6","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.ctrv.2015.10.001","volume":"41","author":"H Mirghani","year":"2015","unstructured":"Mirghani H, Amen F, Tao Y et al (2015) Increased radiosensitivity of HPV-positive head and neck cancers: molecular basis and therapeutic perspectives. Cancer Treat Rev 41(10):844\u2013852. https:\/\/doi.org\/10.1016\/j.ctrv.2015.10.001","journal-title":"Cancer Treat Rev"},{"issue":"9","key":"3134_CR7","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1007\/s00066-014-0605-5","volume":"190","author":"A Arenz","year":"2014","unstructured":"Arenz A, Ziemann F, Mayer C et al (2014) Increased radiosensitivity of HPV-positive head and neck cancer cell lines due to cell cycle dysregulation and induction of apoptosis. Strahlenther Onkol 190(9):839\u2013846. https:\/\/doi.org\/10.1007\/s00066-014-0605-5","journal-title":"Strahlenther Onkol"},{"key":"3134_CR8","doi-asserted-by":"publisher","first-page":"188","DOI":"10.3389\/fimmu.2020.00188","volume":"11","author":"AR Garbuglia","year":"2020","unstructured":"Garbuglia AR, Lapa D, Sias C et al (2020) The use of both therapeutic and prophylactic vaccines in the therapy of papillomavirus disease. Front Immunol 11:188. https:\/\/doi.org\/10.3389\/fimmu.2020.00188","journal-title":"Front Immunol"},{"issue":"4","key":"3134_CR9","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1097\/IGC.0000000000001235","volume":"28","author":"P Basu","year":"2018","unstructured":"Basu P, Mehta A, Jain M et al (2018) A randomized phase 2 study of ADXS11-001 listeria monocytogenes-listeriolysin O immunotherapy with or without cisplatin in treatment of advanced cervical cancer. Int J Gynecol Cancer 28(4):764\u2013772. https:\/\/doi.org\/10.1097\/IGC.0000000000001235","journal-title":"Int J Gynecol Cancer"},{"issue":"10008","key":"3134_CR10","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1016\/S0140-6736(15)00239-1","volume":"386","author":"CL Trimble","year":"2015","unstructured":"Trimble CL, Morrow MP, Kraynyak KA et al (2015) Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2\/3: a randomised, double-blind, placebo-controlled phase 2b trial. The Lancet 386(10008):2078\u20132088. https:\/\/doi.org\/10.1016\/S0140-6736(15)00239-1","journal-title":"The Lancet"},{"issue":"12","key":"3134_CR11","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1089\/hum.2014.024","volume":"25","author":"R Rosales","year":"2014","unstructured":"Rosales R, L\u00f3pez-Contreras M, Rosales C et al (2014) Regression of human papillomavirus intraepithelial lesions is induced by MVA E2 therapeutic vaccine. Hum Gene Ther 25(12):1035\u20131049. https:\/\/doi.org\/10.1089\/hum.2014.024","journal-title":"Hum Gene Ther"},{"issue":"10","key":"3134_CR12","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/nrd4278","volume":"13","author":"U Sahin","year":"2014","unstructured":"Sahin U, Karik\u00f3 K, T\u00fcreci \u00d6 (2014) mRNA-based therapeutics\u2013developing a new class of drugs. Nat Rev Drug Discov 13(10):759\u2013780. https:\/\/doi.org\/10.1038\/nrd4278","journal-title":"Nat Rev Drug Discov"},{"issue":"9","key":"3134_CR13","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2019.1629259","volume":"8","author":"C Grunwitz","year":"2019","unstructured":"Grunwitz C, Salomon N, Vascotto F et al (2019) HPV16 RNA-LPX vaccine mediates complete regression of aggressively growing HPV-positive mouse tumors and establishes protective T cell memory. Oncoimmunology 8(9):e1629259. https:\/\/doi.org\/10.1080\/2162402X.2019.1629259","journal-title":"Oncoimmunology"},{"issue":"7607","key":"3134_CR14","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/nature18300","volume":"534","author":"LM Kranz","year":"2016","unstructured":"Kranz LM, Diken M, Haas H et al (2016) Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature 534(7607):396\u2013401. https:\/\/doi.org\/10.1038\/nature18300","journal-title":"Nature"},{"issue":"13","key":"3134_CR15","doi-asserted-by":"publisher","first-page":"4009","DOI":"10.1182\/blood-2006-04-015024","volume":"108","author":"S Holtkamp","year":"2006","unstructured":"Holtkamp S, Kreiter S, Selmi A et al (2006) Modification of antigen-encoding RNA increases stability, translational efficacy, and T-cell stimulatory capacity of dendritic cells. Blood 108(13):4009\u20134017. https:\/\/doi.org\/10.1182\/blood-2006-04-015024","journal-title":"Blood"},{"issue":"8","key":"3134_CR16","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/gt.2010.52","volume":"17","author":"AN Kuhn","year":"2010","unstructured":"Kuhn AN, Diken M, Kreiter S et al (2010) Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther 17(8):961\u2013971. https:\/\/doi.org\/10.1038\/gt.2010.52","journal-title":"Gene Ther"},{"issue":"1","key":"3134_CR17","doi-asserted-by":"publisher","first-page":"309","DOI":"10.4049\/jimmunol.180.1.309","volume":"180","author":"S Kreiter","year":"2008","unstructured":"Kreiter S, Selmi A, Diken M et al (2008) Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals. J Immunol 180(1):309\u2013318. https:\/\/doi.org\/10.4049\/jimmunol.180.1.309","journal-title":"J Immunol"},{"issue":"5","key":"3134_CR18","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s00262-008-0596-0","volume":"58","author":"C-W Tseng","year":"2009","unstructured":"Tseng C-W, Trimble C, Zeng Q et al (2009) Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts. Cancer Immunol Immunother 58(5):737\u2013748. https:\/\/doi.org\/10.1007\/s00262-008-0596-0","journal-title":"Cancer Immunol Immunother"},{"issue":"2","key":"3134_CR19","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.ymthe.2017.11.011","volume":"26","author":"M-C Chang","year":"2018","unstructured":"Chang M-C, Chen Y-L, Lin H-W et al (2018) Irradiation enhances abscopal anti-tumor effects of antigen-specific immunotherapy through regulating tumor microenvironment. Mol Ther 26(2):404\u2013419. https:\/\/doi.org\/10.1016\/j.ymthe.2017.11.011","journal-title":"Mol Ther"},{"issue":"9","key":"3134_CR20","doi-asserted-by":"publisher","first-page":"2242","DOI":"10.1002\/eji.1830230929","volume":"23","author":"MC Feltkamp","year":"1993","unstructured":"Feltkamp MC, Smits HL, Vierboom MP et al (1993) Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. Eur J Immunol 23(9):2242\u20132249. https:\/\/doi.org\/10.1002\/eji.1830230929","journal-title":"Eur J Immunol"},{"issue":"6","key":"3134_CR21","doi-asserted-by":"publisher","first-page":"1336","DOI":"10.1158\/1535-7163.MCT-14-1015","volume":"14","author":"M Mondini","year":"2015","unstructured":"Mondini M, Nizard M, Tran T et al (2015) Synergy of radiotherapy and a cancer vaccine for the treatment of hpv-associated head and neck cancer. Mol Cancer Ther 14(6):1336\u20131345. https:\/\/doi.org\/10.1158\/1535-7163.MCT-14-1015","journal-title":"Mol Cancer Ther"},{"issue":"1","key":"3134_CR22","doi-asserted-by":"publisher","first-page":"350","DOI":"10.4049\/jimmunol.169.1.350","volume":"169","author":"S Zwaveling","year":"2002","unstructured":"Zwaveling S, Mota SCF, Nouta J et al (2002) Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides. J Immunol 169(1):350\u2013358","journal-title":"J Immunol"},{"issue":"1","key":"3134_CR23","first-page":"21","volume":"56","author":"KY Lin","year":"1996","unstructured":"Lin KY, Guarnieri FG, Staveley-O\u2019Carroll KF et al (1996) Treatment of established tumors with a novel vaccine that enhances major histocompatibility class II presentation of tumor antigen. Cancer Res 56(1):21\u201326","journal-title":"Cancer Res"},{"issue":"8","key":"3134_CR24","doi-asserted-by":"publisher","first-page":"847","DOI":"10.2217\/IMT.15.58","volume":"7","author":"MJ Gough","year":"2015","unstructured":"Gough MJ, Crittenden MR, Young KH (2015) Comparing equals when evaluating immunotherapy with different doses and fractions of radiation therapy. Immunotherapy 7(8):847\u2013849. https:\/\/doi.org\/10.2217\/IMT.15.58","journal-title":"Immunotherapy"},{"issue":"1","key":"3134_CR25","doi-asserted-by":"publisher","first-page":"1771925","DOI":"10.1080\/2162402X.2020.1771925","volume":"9","author":"N Salomon","year":"2020","unstructured":"Salomon N, Vascotto F, Selmi A et al (2020) A liposomal RNA vaccine inducing neoantigen-specific CD4+ T cells augments the antitumor activity of local radiotherapy in mice. Oncoimmunology 9(1):1771925. https:\/\/doi.org\/10.1080\/2162402X.2020.1771925","journal-title":"Oncoimmunology"},{"key":"3134_CR26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/978-1-4939-6481-9_14","volume":"1499","author":"M Diken","year":"2017","unstructured":"Diken M, Vormehr M, Grunwitz C et al (2017) Discovery and subtyping of neo-epitope specific T-cell responses for cancer immunotherapy: addressing the mutanome. Methods Mol Biol 1499:223\u2013236. https:\/\/doi.org\/10.1007\/978-1-4939-6481-9_14","journal-title":"Methods Mol Biol"},{"issue":"17","key":"3134_CR27","doi-asserted-by":"publisher","first-page":"5379","DOI":"10.1158\/1078-0432.CCR-09-0265","volume":"15","author":"MZ Dewan","year":"2009","unstructured":"Dewan MZ, Galloway AE, Kawashima N et al (2009) Fractionated but not single-dose radiotherapy induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody. Clin Cancer Res 15(17):5379\u20135388. https:\/\/doi.org\/10.1158\/1078-0432.CCR-09-0265","journal-title":"Clin Cancer Res"},{"issue":"6","key":"3134_CR28","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nrclinonc.2016.211","volume":"14","author":"RR Weichselbaum","year":"2017","unstructured":"Weichselbaum RR, Liang H, Deng L et al (2017) Radiotherapy and immunotherapy: a beneficial liaison? Nat Rev Clin Oncol 14(6):365\u2013379. https:\/\/doi.org\/10.1038\/nrclinonc.2016.211","journal-title":"Nat Rev Clin Oncol"},{"issue":"7764","key":"3134_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","volume":"571","author":"F Alfei","year":"2019","unstructured":"Alfei F, Kanev K, Hofmann M et al (2019) TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571(7764):265\u2013269. https:\/\/doi.org\/10.1038\/s41586-019-1326-9","journal-title":"Nature"},{"key":"3134_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1324-y","author":"AC Scott","year":"2019","unstructured":"Scott AC, D\u00fcndar F, Zumbo P et al (2019) TOX is a critical regulator of tumour-specific T cell differentiation. Nature. https:\/\/doi.org\/10.1038\/s41586-019-1324-y","journal-title":"Nature"},{"issue":"21","key":"3134_CR31","doi-asserted-by":"publisher","first-page":"7985","DOI":"10.1158\/0008-5472.CAN-04-1525","volume":"64","author":"CT Garnett","year":"2004","unstructured":"Garnett CT, Palena C, Chakraborty M et al (2004) Sublethal irradiation of human tumor cells modulates phenotype resulting in enhanced killing by cytotoxic T lymphocytes. Cancer Res 64(21):7985\u20137994. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-1525","journal-title":"Cancer Res"},{"key":"3134_CR32","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3389\/fimmu.2018.00847","volume":"9","author":"F Castro","year":"2018","unstructured":"Castro F, Cardoso AP, Gon\u00e7alves RM et al (2018) Interferon-gamma at the crossroads of tumor immune surveillance or evasion. Front Immunol 9:847. https:\/\/doi.org\/10.3389\/fimmu.2018.00847","journal-title":"Front Immunol"},{"issue":"12","key":"3134_CR33","doi-asserted-by":"publisher","first-page":"4328","DOI":"10.1158\/0008-5472.CAN-04-0073","volume":"64","author":"M Chakraborty","year":"2004","unstructured":"Chakraborty M, Abrams SI, Coleman CN et al (2004) External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 64(12):4328\u20134337. https:\/\/doi.org\/10.1158\/0008-5472.CAN-04-0073","journal-title":"Cancer Res"},{"issue":"8","key":"3134_CR34","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1038\/sj.mt.6300149","volume":"15","author":"GW Ye","year":"2007","unstructured":"Ye GW, Park J-B, Park Y-J et al (2007) Increased sensitivity of radiated murine cervical cancer tumors to E7 subunit vaccine-driven CTL-mediated killing induces synergistic anti-tumor activity. Mol Ther 15(8):1564\u20131570. https:\/\/doi.org\/10.1038\/sj.mt.6300149","journal-title":"Mol Ther"},{"key":"3134_CR35","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.3389\/fimmu.2018.01591","volume":"9","author":"Y Li","year":"2018","unstructured":"Li Y, Patel SP, Roszik J et al (2018) Hypoxia-driven immunosuppressive metabolites in the tumor microenvironment: new approaches for combinational immunotherapy. Front Immunol 9:1591. https:\/\/doi.org\/10.3389\/fimmu.2018.01591","journal-title":"Front Immunol"},{"issue":"2","key":"3134_CR36","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1006\/gyno.1998.5163","volume":"71","author":"MA Varia","year":"1998","unstructured":"Varia MA, Calkins-Adams DP, Rinker LH et al (1998) Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecol Oncol 71(2):270\u2013277. https:\/\/doi.org\/10.1006\/gyno.1998.5163","journal-title":"Gynecol Oncol"},{"issue":"7","key":"3134_CR37","doi-asserted-by":"publisher","first-page":"1744","DOI":"10.1016\/j.cell.2018.10.028","volume":"175","author":"N van Montfoort","year":"2018","unstructured":"van Montfoort N, Borst L, Korrer MJ et al (2018) NKG2A blockade potentiates CD8 T cell immunity induced by cancer vaccines. Cell 175(7):1744-1755.e15. https:\/\/doi.org\/10.1016\/j.cell.2018.10.028","journal-title":"Cell"},{"issue":"9","key":"3134_CR38","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1038\/sj.gt.3301160","volume":"7","author":"TL Wang","year":"2000","unstructured":"Wang TL, Ling M, Shih IM et al (2000) Intramuscular administration of E7-transfected dendritic cells generates the most potent E7-specific anti-tumor immunity. Gene Ther 7(9):726\u2013733. https:\/\/doi.org\/10.1038\/sj.gt.3301160","journal-title":"Gene Ther"},{"issue":"7549","key":"3134_CR39","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/nature14426","volume":"520","author":"S Kreiter","year":"2015","unstructured":"Kreiter S, Vormehr M, van de Roemer N et al (2015) Mutant MHC class II epitopes drive therapeutic immune responses to cancer. Nature 520(7549):692\u2013696. https:\/\/doi.org\/10.1038\/nature14426","journal-title":"Nature"},{"issue":"5","key":"3134_CR40","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41551-019-0378-3","volume":"3","author":"KE Lindsay","year":"2019","unstructured":"Lindsay KE, Bhosle SM, Zurla C et al (2019) Visualization of early events in mRNA vaccine delivery in non-human primates via PET-CT and near-infrared imaging. Nat Biomed Eng 3(5):371\u2013380. https:\/\/doi.org\/10.1038\/s41551-019-0378-3","journal-title":"Nat Biomed Eng"},{"issue":"172","key":"3134_CR41","doi-asserted-by":"publisher","first-page":"172ra20","DOI":"10.1126\/scitranslmed.3004888","volume":"5","author":"F Sandoval","year":"2013","unstructured":"Sandoval F, Terme M, Nizard M et al (2013) Mucosal imprinting of vaccine-induced CD8+ T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med 5(172):172ra20. https:\/\/doi.org\/10.1126\/scitranslmed.3004888","journal-title":"Sci Transl Med"},{"issue":"6944","key":"3134_CR42","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/nature01726","volume":"424","author":"JR Mora","year":"2003","unstructured":"Mora JR, Bono MR, Manjunath N et al (2003) Selective imprinting of gut-homing T cells by Peyer\u2019s patch dendritic cells. Nature 424(6944):88\u201393. https:\/\/doi.org\/10.1038\/nature01726","journal-title":"Nature"},{"key":"3134_CR43","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-001326","author":"E Beyranvand Nejad","year":"2020","unstructured":"Beyranvand Nejad E, Labrie C, Abdulrahman Z et al (2020) Lack of myeloid cell infiltration as an acquired resistance strategy to immunotherapy. J Immunother Cancer. https:\/\/doi.org\/10.1136\/jitc-2020-001326","journal-title":"J Immunother Cancer"},{"issue":"1","key":"3134_CR44","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1038\/s41467-017-01566-5","volume":"8","author":"H Liang","year":"2017","unstructured":"Liang H, Deng L, Hou Y et al (2017) Host STING-dependent MDSC mobilization drives extrinsic radiation resistance. Nat Commun 8(1):1736. https:\/\/doi.org\/10.1038\/s41467-017-01566-5","journal-title":"Nat Commun"},{"issue":"7764","key":"3134_CR45","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","volume":"571","author":"O Khan","year":"2019","unstructured":"Khan O, Giles JR, McDonald S et al (2019) TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571(7764):211\u2013218. https:\/\/doi.org\/10.1038\/s41586-019-1325-x","journal-title":"Nature"},{"key":"3134_CR46","unstructured":"Radiotherapy dose fractionation, third edition | The Royal College of Radiologists. https:\/\/www.rcr.ac.uk\/publication\/radiotherapy-dose-fractionation-third-edition. Accessed 10 Dec 2019"},{"issue":"12","key":"3134_CR47","doi-asserted-by":"publisher","first-page":"7516","DOI":"10.4049\/jimmunol.174.12.7516","volume":"174","author":"AA Lugade","year":"2005","unstructured":"Lugade AA, Moran JP, Gerber SA et al (2005) Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. J Immunol 174(12):7516\u20137523. https:\/\/doi.org\/10.4049\/jimmunol.174.12.7516","journal-title":"J Immunol"},{"issue":"3","key":"3134_CR48","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1182\/blood-2009-02-206870","volume":"114","author":"Y Lee","year":"2009","unstructured":"Lee Y, Auh SL, Wang Y et al (2009) Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114(3):589\u2013595. https:\/\/doi.org\/10.1182\/blood-2009-02-206870","journal-title":"Blood"},{"issue":"1","key":"3134_CR49","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.semradonc.2014.07.009","volume":"25","author":"B Burnette","year":"2015","unstructured":"Burnette B, Weichselbaum RR (2015) The immunology of ablative radiation. Semin Radiat Oncol 25(1):40\u201345. https:\/\/doi.org\/10.1016\/j.semradonc.2014.07.009","journal-title":"Semin Radiat Oncol"},{"issue":"5","key":"3134_CR50","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.immuni.2014.10.019","volume":"41","author":"L Deng","year":"2014","unstructured":"Deng L, Liang H, Xu M et al (2014) STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41(5):843\u2013852. https:\/\/doi.org\/10.1016\/j.immuni.2014.10.019","journal-title":"Immunity"},{"issue":"7668","key":"3134_CR51","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature23470","volume":"548","author":"SM Harding","year":"2017","unstructured":"Harding SM, Benci JL, Irianto J et al (2017) Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548(7668):466\u2013470. https:\/\/doi.org\/10.1038\/nature23470","journal-title":"Nature"},{"issue":"6260","key":"3134_CR52","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1126\/science.aab3291","volume":"350","author":"L Lau","year":"2015","unstructured":"Lau L, Gray EE, Brunette RL et al (2015) DNA tumor virus oncogenes antagonize the cGAS-STING DNA-sensing pathway. Science 350(6260):568\u2013571. https:\/\/doi.org\/10.1126\/science.aab3291","journal-title":"Science"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-021-03134-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-021-03134-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-021-03134-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T16:25:03Z","timestamp":1658161503000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-021-03134-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,31]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["3134"],"URL":"https:\/\/doi.org\/10.1007\/s00262-021-03134-9","relation":{},"ISSN":["0340-7004","1432-0851"],"issn-type":[{"value":"0340-7004","type":"print"},{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,31]]},"assertion":[{"value":"23 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 December 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 December 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"M.D. and S.K. are employees of TRON gGmbH and BioNTech SE (Mainz, Germany). U.S., M.D., S.K., C.G., N.S. and F.V. are inventors of patents and patent applications related to this study. U.S. and \u00d6.T. are members of the management board of BioNTech SE and hold shares in BioNTech SE. U.S. holds shares in TRON gGmbH. All other authors have no potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Mice were kept in accordance with federal and state policies on animal research at BioNTech SE and experiments approved by the regulatory authorities for animal welfare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Attached.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}