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Epitranscriptomics modifier pentostatin indirectly triggers Toll-like receptor 3 and can enhance immune infiltration in tumors

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اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • Publisher Information:
      Nature Publishing Group 2022-03-01
    • نبذة مختصرة :
      The adenosine deaminase inhibitor 2'-deoxycoformycin (pentostatin, Nipent) has been used since 1982 to treat leukemia and lymphoma, but its mode of action is still unknown. Pentostatin was reported to decrease methylation of cellular RNA. We discovered that RNA extracted from pentostatin-treated cells or mice has enhanced immunostimulating capacities. Accordingly, we demonstrated in mice that the anticancer activity of pentostatin required Toll-like receptor 3, the type I interferon receptor, and T cells. Upon systemic administration of pentostatin, type I interferon is produced locally in tumors, resulting in immune cell infiltration. We combined pentostatin with immune checkpoint inhibitors and observed synergistic anti-cancer activities. Our work identifies pentostatin as a new class of an anticancer immunostimulating drug that activates innate immunity within tumor tissues and synergizes with systemic T cell therapies. Keywords: Nipent; TLR3; cold tumor; epitranscriptomics; hot tumor; immune checkpoint inhibitors; interferon; methylation index; pentostatin; tumor microenvironment.
    • الموضوع:
      Dermatology Clinic; 610 Medicine & health; Drug Discovery, Pharmacology, Genetics, Molecular Biology, Molecular Medicine; Journal Article; PeerReviewed; info:eu-repo/semantics/article; info:eu-repo/semantics/acceptedVersion
    • Availability:
      Open access content. Open access content
      info:eu-repo/semantics/openAccess
      Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
      http://creativecommons.org/licenses/by-nc-nd/4.0
      info:eu-repo/semantics/openAccess
    • Note:
      application/pdf
      info:doi/10.5167/uzh-209616
      English
    • Other Numbers:
      CHUZH oai:www.zora.uzh.ch:209616
      https://www.zora.uzh.ch/id/eprint/209616/1/8._Epitranscriptomics_1-s2.0-S1525001621004779-main.pdf
      info:doi/10.5167/uzh-209616
      info:doi/10.1016/j.ymthe.2021.09.022
      info:pmid/34563676
      urn:issn:1525-0016
      1443041316
    • Contributing Source:
      HAUPTBIBLIOTHEK UNIV OF ZURICH
      From OAIster®, provided by the OCLC Cooperative.
    • الرقم المعرف:
      edsoai.on1443041316
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