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However, the therapeutic benefits of ITV are limited by obstacles such as insufficient antigen loading, inadequate immune system activation, and immunosuppressive tumor microenvironments (TME). Herein, a tumor microenvironment\u2010activated hydrogel platform (TED\u2010Gel) with programmed drug release property is constructed for cascaded amplification of the anti\u2010tumor immune response elicited by ITV. Both doxorubicin (Dox) and cytosine\u2010phosphate\u2010guanosine oligodeoxynucleotides (CpG) are released first, in which Dox induces immunogenic tumor cell death causing additional tumor antigen release and leading the dying primary tumor cells into autologous tumor vaccine, and the released CpG promotes antigen presenting cell activation. Subsequently, the decomposed scaffold materials in conjunction with CpG, turn the anti\u2010inflammatory M2\u2010like macrophages into the M1 type, reversing the immunosuppressive TME. With decomposition of the TED\u2010Gel, large amounts of macromolecule anti\u2010PD\u2010L1 antibodies are liberated, reinvigorating the exhausted effector T cells. In vivo studies demonstrate that TED\u2010Gel significantly inhibits the primary, distant and rechallenged tumor growth. Overall, the simple and powerful TED\u2010Gel provides an alternative strategy for the future development of tumor vaccines with broad application.<\/jats:p>","DOI":"10.1002\/smll.202107061","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T02:55:29Z","timestamp":1667444129000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Tumor Microenvironment\u2010Activated Hydrogel Platform with Programmed Release Property Evokes a Cascade\u2010Amplified Immune Response against Tumor Growth, Metastasis and Recurrence"],"prefix":"10.1002","volume":"18","author":[{"given":"Songlin","family":"Gong","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University  Chengdu 610041 P. R. 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