2026-04-28T21:35:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/176962025-03-20T10:48:03Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Fueyo-Marcos, Elena author Lopez-Pernas, Gema author Fustero-Torre, Coral author Antón, Marta Elena author Al-Shahrour, Fatima author Fernández-Capetillo, Oscar author Murga, Matilde author 2023-03-22 Antibodies 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. Aging (Albany NY) . 2023;15(6):1791-1807. http://hdl.handle.net/20.500.12105/17696 36947705 10.18632/aging.204598 1945-4589 Aging PD-L1ATTAC mice reveal the potential of depleting PD-L1 expressing cells in cancer therapy.