{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T19:01:37Z","timestamp":1774378897337,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Overcoming resistance to immune checkpoint inhibitors (ICIs) remains a critical challenge in the treatment for hepatocellular carcinoma (HCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Our study evaluated the combined efficacy of the recombinant human adenovirus type 5 (H101) and an anti-PD-L1 antibody (APA) in C57BL\/6N mouse model. Gene expression of STAT1 and CD274 (PD-L1) was analyzed by qPCR, and protein levels of PD-L1 and p-STAT1 were assessed via western blot and immunohistochemistry. IFN-\u03b3 secretion and immune cell infiltration were measured by ELISA and flow cytometry, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , H101 inhibited the proliferation and invasion and IFN-\u03b3 induced apoptosis in HCC cells, with IFN-\u03b3 upregulating the expression of STAT1 and CD274. Transfection with si-STAT1 significantly reduced the levels of both STAT1 and CD274\/PD-L1.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , the combination of H101 and APA demonstrated stronger anti-tumor activity, with upregulated IFN-\u03b3 expression and increased infiltration level of CD8+ T cell. Notably, si-STAT1 transfection reduced the expression of p-STAT1 and PD-L1, thereby diminishing the efficacy of both APA monotherapy and the H101+APA combination treatment. The combination therapy significantly reshaped the tumor microenvironment (TME) after si-STAT1 transfection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combination of H101 and APA exhibited excellent anti-HCC efficacy, which may reshape the TME partially through the IFN-\u03b3\/STAT1\/PD-L1 axis. These findings provide a promising strategy to overcome resistance to ICIs in HCC treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1746243","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T16:00:26Z","timestamp":1774368026000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant human adenovirus type 5 synergizes with anti-PD-L1 antibody to promote anti-hepatocellular carcinoma effects through multilevel remodeling of the immune microenvironment"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiu","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Oncology, Changzhou City Fourth People\u2019s Hospital","place":["Changzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Oncology, Changzhou City Fourth 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