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Recent research has increasingly highlighted RT's potential to indirectly enhance antitumor immunity. However, this immune activation alone often fails to generate sustained systemic antitumor responses. In this study, we aimed to investigate the antitumor effects of combining cholesterolized toll\u2010like receptor 7 (TLR7) agonist liposomes, specifically 1V209\u2010Cho\u2010Lip, with RT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Mouse tumor models were used to assess the impact of combining 1V209\u2010Cho\u2010Lip with RT on tumor progression and modification of the tumor microenvironment. In vitro, primary mouse bone marrow\u2010derived dendritic cells (BMDCs) were utilized to investigate changes in function and the activated pathways through RNA sequencing. Additionally, we explored the role of oxidized mitochondrial DNA (ox\u2010mtDNA) released from irradiated tumor cells as a damage\u2010associated molecular pattern in modulating immune responses. The involvement of interleukin\u20101\u03b2 (IL\u20101\u03b2) and the inflammasome pathway in the antitumor efficacy of the combined treatment was evaluated using\n                      <jats:italic toggle=\"yes\">\n                        Il\u20101\u03b2\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and cysteinyl aspartate specific proteinase 1 knockout (\n                      <jats:italic toggle=\"yes\">\n                        Casp1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      ) mouse models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The combination of 1V209\u2010Cho\u2010Lip and RT significantly inhibited tumor growth and induced antitumor immunity in tumor models. This combination therapy enhanced maturation, antigen presentation and IL\u20101\u03b2 secretion of dendritic cells (DCs) in vitro. Ox\u2010mtDNA released from irradiated tumor cells synergized with 1V209\u2010Cho\u2010Lip to activate the inflammasome pathway in DCs. The antitumor effect of the combined therapy was significantly reduced in\n                      <jats:italic toggle=\"yes\">\n                        Il\u20101\u03b2\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">\n                        Casp1\n                        <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      <\/jats:italic>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study suggests that the combination of 1V209\u2010Cho\u2010Lip with RT might be a promising antitumor strategy and further studies are warranted to explore the clinical relevance of this combination therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cac2.70024","type":"journal-article","created":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T07:00:41Z","timestamp":1744268441000},"page":"794-812","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Enhancing antitumor immunity through the combination of cholesterolized TLR7 agonist liposomes and radiotherapy: a role for IL\u20101\u03b2 and the inflammasome pathway"],"prefix":"10.34133","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9842-8990","authenticated-orcid":false,"given":"Xuejiao","family":"Han","sequence":"first","affiliation":[{"name":"West China Hospital","place":["Chengdu, P. 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