title: Enhancing the anticancer effects of 5-fluorouracil: current challenges and future perspectives.
abstract: 5-Flurouracil (5-FU), a pyrimidine analog, was originally designed to prevent tumor cell growth. However, since the identification of its tumor inhibitory activity in 1957, substantial evidence has demonstrated that 5-FU could also harness the host immune system to prevent cancer progression. 5-FU sensitizes tumor cells to Natural Killer (NK) and CD8 T cell-driven cytotoxicity. We have also recently shown that 5-FU could selectively eliminate Myeloid Derived Suppressor Cells (MDSCs), which accumulate during cancer progression and compromise anticancer immune responses. The ability of 5-FU to trigger direct tumor cell death, enhance immune effector cell activation and eliminate immunosuppressive MDSCs explains its capacity to relieve tumor-induced immunosuppression and restore anticancer immune responses. Combination therapies using 5-FU with other chemotherapeutic agents, immunomodulators, or vaccines have further enhanced the clinical benefit of 5-FU. Here, we discuss how the increased understanding of the immune-driven effects of 5-FU prompts the design of relevant cancer chemoimmunotherapy strategies.
authors.forename: Francois
authors.initials: F
authors.lastname: Ghiringhelli
authors.affiliation: INSERM, U866; Centre Georges François Leclerc; Université de Bourgogne, Dijon, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D005472:Fluorouracil