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However, in previous anti\u2010tumor studies of combined photo\/immunotherapy, the tumor apoptosis pathway is widely regarded as an independent process, which led to an incomplete understanding of the anti\u2010tumor mechanisms of the immune system during phototherapy. Herein, the decisive role of immune activation for the anti\u2010tumor effect of phototherapy and its specific mechanism, are investigated by preparing a melanin@chlorin e6@hyaluronic acid and oxidized <jats:italic>Bletilla striata<\/jats:italic> polysaccharide@NO\u2010donor (MCH\u2010OBN) nanoplatform, which integrated significant immune activation by phototherapy. The comparison of anti\u2010tumor effects between wild\u2010type mice and immunodeficient mice showed that effective phototherapy provided by the MCH\u2010OBN can not independently kill tumor cells in vivo, as it significantly depends on the immune activation. Furthermore, the activated immune system is demonstrated to destroy the tumor cell \u201cbarrier protection\u201d by inhibiting the growth of cancer\u2010associated fibroblasts (CAFs), thereby ensuring the damage of heat, reactive oxygen species (ROS), and other components of phototherapy to the tumor. Thus, this work reveals for the first time the biological consequences of immune activation that determine the anti\u2010tumor effect of phototherapy by regulating CAF proliferation, which is of great significance for optimizing anti\u2010tumor clinical treatments through phototherapy.<\/jats:p>","DOI":"10.1002\/adfm.202315551","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T06:39:46Z","timestamp":1707892786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Activated Immune System Determines In Vivo Anti\u2010Tumor Effect of Phototherapy by Inhibiting Cancer\u2010Associated Fibroblasts"],"prefix":"10.1002","volume":"34","author":[{"given":"Mengchao","family":"Ding","sequence":"first","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"},{"name":"School of Biomedical Sciences and Engineering South China University of Technology  Guangzhou 510650 China"}]},{"given":"Haoyu","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Carlos F.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"3B's Research Group\u2010Research Institute on Biomaterials Biodegradables and Biomimetics University of Minho Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine Parque de Ci\u00eancia e Tecnologia Zona Industrial da Gandra \u2013 Avepark  Guimar\u00e3es 4805\u2010017 Portugal"},{"name":"ICVS\/3B's \u2013 Portuguese Government Associate Laboratory University of Minho  Guimar\u00e3es 4800\u2010058 Portugal"}]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"3B's Research Group\u2010Research Institute on Biomaterials Biodegradables and Biomimetics University of Minho Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine Parque de Ci\u00eancia e Tecnologia Zona Industrial da Gandra \u2013 Avepark  Guimar\u00e3es 4805\u2010017 Portugal"},{"name":"ICVS\/3B's \u2013 Portuguese Government Associate Laboratory University of Minho  Guimar\u00e3es 4800\u2010058 Portugal"}]},{"given":"Lijuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Innovation Platform of Marine Drug Screening &amp; Evaluation Qingdao National Laboratory for Marine Science and Technology Qingdao 266237 China"}]},{"given":"Fenglan","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University  Qingdao 266109 China"}]},{"given":"Yaqian","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine Qingdao Agricultural University  Qingdao 266109 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