417P Nucleotide sanitation as treg survival and proliferation mechanism in hypoxic conditions

Immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, therapeutic responses are highly variable, in part due to immunosuppressive resistance mechanisms driven by specific cell populations, including CD4+ regulatory T cells (Treg). Our study has revealed the overexpression of the nucleotide sanitizer enzyme DNPH1 in Treg cells in ICB non-responder patients. DNPH1 hydrolyzes modified nucleotide hydroxymethyldeoxyuridine (hmdU) monophosphate, preventing its integration into the DNA.