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Its antitumor efficacy and mechanisms were evaluated in syngeneic (MC38, CT26) and humanized mouse models. Molecular analyses (Western blot, immunofluorescence, and qPCR) elucidated signaling pathways. Immunological outcomes were assessed via flow cytometry and in vitro co-culture assays. Combination therapies with anti-PD-1 or CAR-T cells were tested in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We demonstrate that ADV-PRK abrogates phosphorylation of both AKT and its downstream effector, the ER calcium channel IP3R3. This suppression drives ER calcium efflux, inducing calreticulin (CRT) translocation to the cell surface. Surface-exposed CRT acts as a potent \u201ceat-me\u201d signal, licensing dendritic cells to prime and activate tumor-specific CD8\u207a T cells, which are essential for efficacy. In vivo, ADV-PRK monotherapy achieved superior tumor control. It demonstrated potent synergy with both anti-PD-1 and CAR-T cell therapy, by remodeling the immune landscape to expand activatable T cells and support adoptive cellular therapy. Its activity in a humanized model confirms translational relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our work delineates a distinct immunomodulatory axis, AKT\u2013IP3R3\u2013Ca\n                      <jats:sup>2<\/jats:sup>\n                      \u207a\u2013CRT, to reverse adenovirus-induced immunosuppression. This provides a translatable, mechanism-based strategy to convert immunologically \u201ccold\u201d tumors into environments receptive to immunotherapy, thereby offering a rational combinatorial approach to overcome resistance and significantly broaden the applicability of current immunotherapies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                    <jats:p>An oncolytic adenovirus delivering the AKT-inhibitory peptide (ADV-PRK) triggers an immunogenic cascade via the AKT\u2013IP3R3\u2013calcium\u2013calreticulin axis. By inducing calreticulin exposure, it arms dendritic cells to prime tumor-specific CD8\u207a T cells, ultimately synergizing with anti-PD-1 or CAR-T therapy against colorectal cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00535-026-02513-2","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T03:09:23Z","timestamp":1788750563000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A PRK-armed oncolytic adenovirus drives calreticulin exposure for dendritic cell licensing to prime antitumor CD8\u207a T cells and synergizes with anti-PD-1 or CAR-T therapy in colorectal cancer"],"prefix":"10.1007","author":[{"given":"Yan","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingkai","family":"Kong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciliang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanqi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huawei","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilei","family":"Xin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingjun","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4753-2648","authenticated-orcid":false,"given":"Junhua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"2513_CR1","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.tips.2023.01.003","volume":"44","author":"AE Shin","year":"2023","unstructured":"Shin AE, Giancotti FG, Rustgi AK. 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