Fueyo-Marcos, ElenaLopez-Pernas, GemaFustero-Torre, CoralAntón, Marta ElenaAl-Shahrour, FatimaFernández-Capetillo, OscarMurga, Matilde2024-02-092024-02-092023-03-22Aging (Albany NY) . 2023;15(6):1791-1807.http://hdl.handle.net/20.500.12105/17696Antibodies targeting the PD-1 receptor and its ligand PD-L1 have shown impressive responses in some tumors of bad prognosis. We hypothesized that, since immunosuppressive cells might present several immune checkpoints on their surface, the selective elimination of PD-L1 expressing cells could be efficacious in enabling the activation of antitumoral immune responses. To address this question, we developed an inducible suicidal knock-in mouse allele of Pd-l1 (PD-L1ATTAC) which allows for the tracking and specific elimination of PD-L1-expressing cells in adult tissues. Consistent with our hypothesis, elimination of PD-L1 expressing cells from the mouse peritoneum increased the septic response to lipopolysaccharide (LPS), due to an exacerbated inflammatory response to the endotoxin. In addition, mice depleted of PD-L1+ cells were resistant to colon cancer peritoneal allografts, which was associated with a loss of immunosuppressive B cells and macrophages, concomitant with an increase in activated cytotoxic CD8 T cells. Collectively, these results illustrate the usefulness of PD-L1ATTAC mice for research in immunotherapy and provide genetic support to the concept of targeting PD-L1 expressing cells in cancer.engNAhttp://creativecommons.org/licenses/by-nc-nd/4.0/Antineoplastic AgentsNeoplasmsMiceAnimalsB7-H1 AntigenImmunotherapyT-Lymphocytes, CytotoxicCell Line, TumorCD8-Positive T-LymphocytesTumor MicroenvironmentAttribution-NonCommercial-NoDerivatives 4.0 Internacional36947705156179110.18632/aging.2045981945-4589Agingopen access