Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases.

Background: The interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. Using N-ethyl-N-nitrosourea mutagenesis, we found a mouse with an activating mutation in oligoadenylate synthetase 2 (Oas2),...

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Publicado en:Breast Cancer Research Vol. 24; no. 1; pp. 1 - 15
Autores principales: Ho, Wing-Hong Jonathan, Law, Andrew M. K., Masle-Farquhar, Etienne, Castillo, Lesley E., Mawson, Amanda, O'Bryan, Moira K., Goodnow, Christopher C., Gallego-Ortega, David, Oakes, Samantha R., Ormandy, Christopher J.
Formato: research Journal Article
Publicado: BioMed Central 5/3/2022
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 5/3/2022
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      pub: BioMed Central
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        10.1186/s13058-022-01525-z
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        atl: Activation of the viral sensor oligoadenylate synthetase 2 (Oas2) prevents pregnancy-driven mammary cancer metastases.
      aug:
        au:
          Ho, Wing-Hong Jonathan
          Law, Andrew M. K.
          Masle-Farquhar, Etienne
          Castillo, Lesley E.
          Mawson, Amanda
          O'Bryan, Moira K.
          Goodnow, Christopher C.
          Gallego-Ortega, David
          Oakes, Samantha R.
          Ormandy, Christopher J.
        affil: Garvan Institute of Medical Research, 384 Victoria Street, 2010, Darlinghurst Sydney, NSW, Australia
      sug:
        subj:
          Breast Neoplasms
          Transferases
          Interferons
          Nucleotides
          Animals
          Mice
          Enzymes
          Female
          Pregnancy
          Female
      ab: Background: The interferon response can influence the primary and metastatic activity of breast cancers and can interact with checkpoint immunotherapy to modulate its effects. Using N-ethyl-N-nitrosourea mutagenesis, we found a mouse with an activating mutation in oligoadenylate synthetase 2 (Oas2), a sensor of viral double stranded RNA, that resulted in an interferon response and prevented lactation in otherwise healthy mice.Methods: To determine if sole activation of Oas2 could alter the course of mammary cancer, we combined the Oas2 mutation with the MMTV-PyMT oncogene model of breast cancer and examined disease progression and the effects of checkpoint immunotherapy using Kaplan-Meier survival analysis with immunohistochemistry and flow cytometry.Results: Oas2 mutation prevented pregnancy from increasing metastases to lung. Checkpoint immunotherapy with antibodies against programmed death-ligand 1 was more effective when the Oas2 mutation was present.Conclusions: These data establish OAS2 as a therapeutic target for agents designed to reduce metastases and increase the effectiveness of checkpoint immunotherapy.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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