{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:34Z","timestamp":1785301234842,"version":"3.55.0"},"reference-count":249,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Therapeutic cancer vaccines are designed to initiate tumor-specific immunity, yet their clinical success depends not only on antigen selection but also on the capacity to overcome the profoundly suppressive tumor microenvironment. Within tumors, abnormal vasculature, hypoxia, nutrient competition, acidic pH, and suppressive myeloid and stromal cells collectively constrain antigen presentation, T-cell priming, trafficking, and effector function, often converting otherwise immunogenic vaccination into an ineffective immune stimulus. Recent advances in neoantigen discovery, dendritic cell engineering, and nucleic acid-based vaccine platforms have improved the precision of antigen delivery, but these gains remain insufficient unless vaccine-induced responses can be sustained and executed within the hostile metabolic and immunologic landscape of the tumor niche. In this context, the tumor microenvironment is not merely a barrier to be overcome, but an active determinant of vaccine outcome that shapes immune editing, promotes exhaustion, and limits intratumoral expansion of cytotoxic lymphocytes. Accordingly, the most promising therapeutic strategies now combine vaccination with checkpoint blockade, radiotherapy, stromal remodeling, or metabolic reprogramming to recondition the tumor ecosystem and permit productive antitumor immunity. Here, we discuss how tumor microenvironmental constraints govern vaccine performance, review emerging platform technologies, and outline combinatorial strategies aimed at converting immune priming into durable tumor control.<\/jats:p>","DOI":"10.3390\/vaccines14080658","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bidirectional Interplay Between Tumor Vaccines and the Tumor Microenvironment: Mechanisms, Cold-to-Hot Conversion, and Combination Strategies"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhangzhou","family":"Shen","sequence":"first","affiliation":[{"name":"Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Provincial Engineering Research Center of Immunotherapy Drugs for Renal Tumors, Medical School, Hubei Polytechnic University, Huangshi 435003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinqin","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Huangshi Maternity and Children\u2019s Health Hospital, Affiliated Maternity and Children\u2019s Health Hospital of Hubei Polytechnic University, Huangshi 435003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Huangshi Maternity and Children\u2019s Health Hospital, Affiliated Maternity and Children\u2019s Health Hospital of Hubei Polytechnic University, Huangshi 435003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-6012","authenticated-orcid":false,"given":"Houqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Animal Sciences, Wenzhou Vocational College of Science and Technology, Wenzhou 325000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Yoon, J., Moon, H., Jeon, Y., Choe, S., and Yoon, H. 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