Uracil-DNA glycosylase deficiency is associated with repressed tumor cell-intrinsic inflammatory signaling and altered sensitivity to exogenous interferons.

ABSTRACT: 2'-deoxyuridine (dU) is a common DNA lesion resulting from cytosine deamination and from dUMP incorporation by DNA polymerases, both of which are prevalent in cancer. The primary mechanism that repairs dU lesions in genomic DNA is base excision repair initiated by Uracil-DNA Glycosylase 2 (UNG2). We generated Ung knockout mouse B16 melanoma cells to investigate the consequences of UNG deficiency in a well-characterized, immunocompetent, syngeneic mouse cancer model. We show that UNG-deficient (ΔUNG) B16 tumors exhibited T cell-dependent, delayed growth in vivo and were more responsive to anti-PD-L1 therapy. Immune profiling revealed reduced CD8⁺ T cell infiltration but augmented IFN-γ-competent effector CD4⁺ T cells in ΔUNG tumors. In vitro, ΔUNG

SUBMITTER: Vendetti FP 

PROVIDER: S-EPMC12754777 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature