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However, the poor response rate is still a formidable challenge of current immunotherapies, especially in solid tumors without sufficient infiltration of immune cells, also known as \u201ccold tumor.\u201d SAR405\u00a0is a highly specific VPS34\u00a0inhibitor and has been suggested as a potential approach converting \u201ccold tumor\u201d into \u201chot tumor\u201d by inhibiting autophagy. In this study, a tri\u2010functional doxorubicin (DOX) plus SAR405\u00a0liposome system is established and further modified with a novel anti\u2010PD\u2010L1\u00a0peptide JY4\u00a0for targeted delivery (DOX\u2010SAR\u2010JY4<jats:sub>LIPO<\/jats:sub>). The data here demonstrate that in a lung cancer xenograft mouse model, by facilitating the tumoral enrichment of both SAR405\u00a0and DOX, DOX\u2010SAR\u2010JY4<jats:sub>LIPO<\/jats:sub> effectively increases the infiltration of cytotoxic lymphocytes in the tumor by synergizing DOX\u2010induced immunogenic cell death (ICD) and SAR405\u2010mediated upregulation of chemokines including CCL5\u00a0and CXCL10. As results, DOX\u2010SAR\u2010JY4<jats:sub>LIPO<\/jats:sub> significantly inhibits tumor growth, metastasis, and resurrection by re\u2010educating immunosuppressive tumor microenvironment. In conclusion, this study not only proves the concept of inhibiting autophagy for better immune infiltration in the tumor but also presents a novel tri\u2010functional liposomal system that overcomes the deficiencies of current therapies and holds great promise in cancer immunotherapy.<\/jats:p>","DOI":"10.1002\/adhm.202202757","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T17:54:40Z","timestamp":1674064480000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Novel Tri\u2010Functional Liposome Re\u2010Educates \u201cCold Tumor\u201d and Abrogates Tumor Growth by Synergizing Autophagy Inhibition and PD\u2010L1 Blockade"],"prefix":"10.1002","volume":"12","author":[{"given":"Fei","family":"Zhou","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica Beijing University of Chinese Medicine  11 Bei San Huan Dong Lu Beijing 100029 China"},{"name":"School of 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