ISG15 pathway knockdown reverses pancreatic cancer cell transformation and decreases murine pancreatic tumor growth via downregulation of PDL-1 expression.
作者： Julian Burks , Alia Fleury , Sarah Livingston , Jill P. Smith
DOI: 10.1007/S00262-019-02422-9
关键词:
摘要: Interferon-stimulated gene 15 (ISG15) is a 15 kDa protein induced by type I interferons (IFN-α and IFN-β) member of the ubiquitin-like superfamily proteins. The ISG15 pathway highly expressed in various malignancies, including pancreatic ductal adenocarcinoma (PDAC), suggesting potential role (free conjugates) carcinogenesis. However, very little known about how may contribute to tumorigenesis. In current study, we demonstrate that knockdown reverses KRAS-associated phenotypes PDAC cells such as increased proliferation colony formation. Furthermore, clustered regularly interspaced short palindromic repeats (CRISPR)-mediated decreased tumor programmed death ligand-1 (PDL-1) expression leading number CD8+ tumor-infiltrating lymphocytes tumor growth. addition, syngeneic subcutaneous mouse model revealed knocking down significantly rate incidence survival rate. Interestingly, knockdown-mediated PDL-1 downregulation tumors efficacy anti-programmed cell protein-1 (PD-1) treatment. combination with anti-PD-1 treatment synergistically lymphocytes. Additionally, alone regulatory T (Tregs) compared wild treated antibody. Overall, these findings suggest strategies target itself or immunotherapy lead improved for patients diagnosed PDAC.
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