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This can be largely attributed to an immune\u2010suppressive tumor microenvironment (TME) manifested as immature myeloid cells and exhausted cytotoxic T lymphocytes. Here, a three\u2010in\u2010one oncolytic adenovirus system PEG\u2010PEI\u2010Adv\u2010Catalase\u2010KillerRed (p\u2010Adv\u2010CAT\u2010KR) has been constructed to multiply, initiate, and enhance immune responses in photodynamic immunotherapy, using genetically\u2010engineered KillerRed as photosensitizer, catalase as in situ oxygen\u2010supplying mediator, and adenovirus as immunostimulatory bio\u2010reproducible carrier. Meanwhile, PEG\u2010PEI is applied to protect adenovirus from circulating immune attack. The administration of p\u2010Adv\u2010CAT\u2010KR induces increased antigen presenting cells, elevated T cell infiltrations, and reduced tumor burden. Further investigation into underlying mechanism indicates that hypoxia inducible factor 1 subunit alpha (Hif\u20101\u03b1) and its downstream PD\u20101\/PD\u2010L1 pathway contribute to the transformation of immune\u2010suppressive TME in cholangiocarcinoma. Collectively, the combination of KillerRed, catalase, and adenovirus brings about multi\u2010amplified antitumor photo\u2010immunity and has the potential to be an effective immunotherapeutic strategy for cholangiocarcinoma.<\/jats:p>","DOI":"10.1002\/smll.202207668","type":"journal-article","created":{"date-parts":[[2023,5,2]],"date-time":"2023-05-02T03:50:52Z","timestamp":1682999452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Three\u2010in\u2010One Oncolytic Adenovirus System Initiates a Synergetic Photodynamic Immunotherapy in Immune\u2010Suppressive Cholangiocarcinoma"],"prefix":"10.1002","volume":"19","author":[{"given":"Jialun","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing 210008 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