Reversing the “cold” tumor microenvironment: the role of neoantigen vaccines in prostate cancer
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Le résumé fourni par la source
Prostate cancer (PCa) is a common malignancy with a “cold” tumor microenvironment (TME) that limits immunotherapy efficacy. Neoantigens from non-synonymous mutations are potential immunotherapeutic targets. We identified the neoantigens map in the RM-1 murine prostate cancer model by the whole exome sequencing. The immunogenicity of the identified neoantigens was subsequently assessed using enzyme-linked immunospot assays. In vivo neoantigen vaccination experiments were finally conducted in mice to assess the antitumoral effect on PCa, and comprehensively understand the intrinsic dynamic mechanisms for reversing "cold" TME. We identified 252 nonsynonymous somatic mutations in RM-1 murine PCa, and the allele frequency of 62 mutations were above 60%. The immunogenicity and specificity of 10 candidate mutations were estimated by immunizing RM-1 mice with neoantigen peptides. Among them, four of these epitopes exhibited the immunogenicity, and three of them ( Med12 D182fs , Stxbp4 A535T and Hp1bp3 L16F ) were proved to have therapeutic efficacy in the PCa murine model. Functional immunological experiments and bulk RNA sequencing indicated a significantly enhanced infiltration and activation of T cells, as well as upregulation of activated immune-related genes, and finally reversed the “cold” TME into “hot”. This study contributed to an unmet therapeutic need for PCa, particularly its potential mechanisms for reversing “cold” TME, which lays the foundation for future application of neoantigen vaccine immunotherapy in prostate cancer.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Reversing the “cold” tumor microenvironment: the role of neoantigen vaccines in prostate cancer
- Date Crossref
- 25/07/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Chinese Academy of Medical Sciences & Peking Union Medical College Beijing Hospital pays non établi dans la noticeUniversité ou école supérieure
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Institute of Hematology & Blood Diseases Hospital pays non établi dans la noticeÉtablissement de santé
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Shandong Provincial Hospital Department of Critical Care Unit pays non établi dans la noticeÉtablissement de santé
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Shandong First Medical University pays non établi dans la noticeUniversité ou école supérieure
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Beijing Hospital Center of Biotherapy pays non établi dans la noticeÉtablissement de santé
Beijing Hospital — Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital et Department of Critical Care Unit — Shandong Provincial Hospital, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.