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However, ICI monotherapy is often ineffective in patients with non-immunogenic tumors that exhibit high level of immunosuppression and low level of tumor infiltrating lymphocytes. To address these limitations, we have investigated a combination of ICIs [anti-PD-1 antibody (\u03b1PD-1), anti-PD-L1 antibody (\u03b1PD-L1), or anti-CTLA-4 antibody (\u03b1CTLA-4)] with several different immune stimulatory oncolytic adenoviruses (Ads) expressing different combinations of antitumor cytokines or immune modulatory factors [e.g., (1) interleukin (IL)-12 and granulocyte-macrophage colony-stimulating factor (GM-CSF; RdB\/IL12\/GMCSF), (2) IL-12 and short hairpin ribonucleic acid (shRNA) targeting vascular endothelial growth factor (RdB\/IL12\/shVEGF), (3) IL-12 and decorin (RdB\/IL12\/DCN), (4) GM-CSF, and thymidine kinase (RdB\/IL12\/GMCSF-TK), or (5) IL-12, GM-CSF, and relaxin (RdB\/IL12\/GMCSF-RLX)] to overcome tumor-induced immunosuppression. Through comparative evaluation of combination therapy regimens, our findings have identified \u03b1PD-1 as the optimal ICI candidate to synergize with different oncolytic Ads to induce potent antitumor immune response against poorly immunological solid tumors.<\/jats:p>","DOI":"10.1186\/s10020-025-01223-4","type":"journal-article","created":{"date-parts":[[2025,5,7]],"date-time":"2025-05-07T08:05:12Z","timestamp":1746605112000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Enhanced potency of immune checkpoint inhibitors against poorly immunological solid tumors by immune stimulatory oncolytic adenoviruses-mediated remodeling of the tumor microenvironment"],"prefix":"10.1186","volume":"31","author":[{"given":"Hyo Min","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-Kyeong","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JinWoo","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayoung","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A-Rum","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Ok","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,7]]},"reference":[{"key":"1223_CR1","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1039\/c5ib00040h","volume":"7","author":"I Acerbi","year":"2015","unstructured":"Acerbi I, et al. 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