title: The MDM2 inhibitor Nutlin-3 modulates dendritic cell-induced T cell proliferation.
abstract: Nutlin-3, a small molecule inhibitor of the MDM2/p53 interaction, has been recently taken into consideration as a promising therapeutic tool for tumor treatment based on its ability to stabilize and activate the p53 transcription factor pathway. Since Nutlin-3 displays non cell-autonomous tumor-suppressor activities, we wanted to investigate its effect on dendritic cell functions, given the central role of these cells in the modulation of the immune response. We found that Nutlin-3 alone slightly affected the levels of major histocompatibility complex and costimulatory molecules and significantly promoted the ability of dendritic cells to stimulate T cells in the mixed lymphocyte reaction. Taken together, our findings suggest that the ability of Nutlin-3 to modulate dendritic cell functions and therefore lymphocyte proliferation might represent an additional important mechanism by which Nutlin-3 exerts its non cell-autonomous tumor-suppression function.
authors.affiliation: Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. chiara.gasparini@burlo.trieste.it
authors.forename: Chiara
authors.initials: C
authors.lastname: Gasparini
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
authors.forename: Giorgio
authors.initials: G
authors.lastname: Zauli
mesh_terms: D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D010879:Piperazines / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007093:Imidazoles; D007155:Immunologic Factors; D010879:Piperazines; C482205:nutlin 3; D051736:Proto-Oncogene Proteins c-mdm2