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<lom:catalog>DOI</lom:catalog>

  
<lom:entry>
  
<lom:langstring xml:lang="x-none">10.1038/s44321-024-00157-4</lom:langstring>

  
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<lom:title>
  
<lom:langstring xml:lang="en">Fibrolytic vaccination against ADAM12 reduces desmoplasia in preclinical pancreatic adenocarcinomas</lom:langstring>

  
</lom:title>

  
<lom:description>
  
<lom:langstring xml:lang="en">A hallmark feature of pancreatic ductal adenocarcinoma (PDAC) is massive intratumoral fibrosis, designated as desmoplasia. Desmoplasia is characterized by the expansion of cancer-associated fibroblasts (CAFs) and a massive increase in extracellular matrix (ECM). During fibrogenesis, distinct genes become reactivated specifically in fibroblasts, e.g., the disintegrin metalloprotease, ADAM12. Previous studies have shown that immunotherapeutic ablation of ADAM12+ cells reduces fibrosis in various organs. In preclinical mouse models of PDAC, we observe ADAM12 expression in CAFs as well as in tumor cells but not in healthy mouse pancreas. Therefore, we tested prophylactic and therapeutic vaccination against ADAM12 in murine PDAC and observed delayed tumor growth along with a reduction in CAFs and tumor desmoplasia. This is furthermore associated with vascular normalization and alleviated tumor hypoxia. The ADAM12 vaccine induces a redistribution of CD8+ T cells within the tumor and cytotoxic responses against ADAM12+ cells. In summary, vaccination against the endogenous fibroblast target ADAM12 effectively depletes CAFs, reduces desmoplasia and delays the growth of murine PDACs. These results provide proof-of-principle for the development of vaccination-based immunotherapies to treat tumor desmoplasia.</lom:langstring>

  
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<lom:language>eng</lom:language>

  
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<lom:langstring xml:lang="en">Animals</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">ADAM12 Protein Metabolism</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Mice</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Cancer Vaccines Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Cancer Vaccines Administration &amp; Dosage</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Pancreatic Neoplasms Pathology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Pancreatic Neoplasms Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Pancreatic Neoplasms Prevention &amp; Control</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Carcinoma Pancreatic Ductal Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Carcinoma, Pancreatic Ductal Pathology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Carcinoma Pancreatic Ductal Therapy</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Vaccination</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Disease Models Animal</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Mice Inbred C57BL</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Cancer-Associated Fibroblasts Metabolism</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Cancer-Associated Fibroblasts Pathology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Cancer-Associated Fibroblasts Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Humans</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">CD8-Positive T-Lymphocytes Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Fibrosis</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Adenocarcinoma Immunology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Adenocarcinoma Pathology</lom:langstring>

  
</lom:keyword>

  
<lom:keyword>
  
<lom:langstring xml:lang="en">Adenocarcinoma Therapy</lom:langstring>

  
</lom:keyword>

  
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<lom:datetime>2025-01-20T08:44:46.034Z</lom:datetime>

  
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<lom:vcard>BEGIN:VCARD
VERSION:3.0
N:Chen;Jing;
FN:Jing Chen
X-ORCID:https://orcid.org/0000-0003-1835-2373
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N:Sobecki;Michal;
FN:Michal Sobecki
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VERSION:3.0
N:Krzywinska;Ewelina;
FN:Ewelina Krzywinska
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N:Thierry;Kevin;
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N:Masmoudi;Mélissa;
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N:Nagarajan;Shunmugam;
FN:Shunmugam Nagarajan
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<lom:vcard>BEGIN:VCARD
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N:Fan;Zheng;
FN:Zheng Fan
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N:He;Jingyi;
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N:Ferapontova;Irina;
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N:Nelius;Eric;
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N:Seehusen;Frauke;
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N:Gotthardt;Dagmar;
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N:Takeda;Norihiko;
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N:Sommer;Lukas;
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<lom:vcard>BEGIN:VCARD
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N:Sexl;Veronika;
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<lom:vcard>BEGIN:VCARD
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N:Münz;Christian;
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N:DeNardo;David;
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N:Hennino;Ana;
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<lom:vcard>BEGIN:VCARD
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N:Stockmann;Christian;
FN:Christian Stockmann
X-ORCID:https://orcid.org/0000-0002-9726-6838
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