RT info:eu-repo/semantics/article
T1 Differential Engraftment of Parental A20 PD-L1 WT and PD-L1 KO Leukemia Cells in Semiallogeneic Recipients in the Context of PD-L1/PD-1 Interaction and NK Cell-Mediated Hybrid Resistance
A1 Río González, María Luisa del
A1 Perez-Simon, Jose-Antonio
A1 Rodríguez Barbosa, José Ignacio
A2 Inmunologia
K1 Inmunología
K1 A20 leukemia cells
K1 CD80
K1 PD-L1
K1 NK cells
K1 PD-1
K1 PD-L2
K1 Hybrid resistance
AB [EN] The contribution of natural killer (NK) cells to tumor rejection in the context of programmed death-ligand 1/programmed death 1 (PD-L1/PD-1) blockade is a matter of intense debate. To elucidate the role of PD-L1 expression on tumor cells and the functional consequences of engaging PD-1 receptor on cytotoxic cells, PD-L1 expression was genetically inactivated and WT or PD-L1-deficient parental tumor cells were adoptively transferred intravenously into F1 recipients. The engraftment of PD-L1-deficient A20 tumor cells in the spleen and liver of F1 recipients was impaired compared with A20 PD-L1 WT tumor counterparts. To elucidate the mechanism responsible for this differential tumor engraftment and determine the relevance of the role of the PD-L1/PD-1 pathway in the interplay of tumor cells/NK cells, a short-term competitive tumor implantation assay in the peritoneal cavity of semiallogeneic F1 recipients was designed. The results presented herein showed that NK cells killed target tumor cells with similar efficiency regardless of PD-L1 expression, whereas PD-L1 expression on A20 tumor cells conferred significant tumor protection against rejection by CD8 T cells confirming the role of the co-inhibitory receptor PD-1 in the modulation of their cytotoxic activity. In summary, PD-L1 expression on A20 leukemia tumor cells modulates CD8 T-cell-mediated responses to tumor-specific antigens but does not contribute to inhibit NK cell-mediated hybrid resistance, which correlates with the inability to detect PD-1 expression on NK cells neither under steady-state conditions nor under inflammatory conditions.
PB Frontiers
LK http://hdl.handle.net/10612/15056
UL http://hdl.handle.net/10612/15056
NO Del Rio, M. L., Perez-Simon, J. A., & Rodriguez-Barbosa, J. I. (2022). Differential Engraftment of Parental A20 PD-L1 WT and PD-L1 KO Leukemia Cells in Semiallogeneic Recipients in the Context of PD-L1/PD-1 Interaction and NK Cell-Mediated Hybrid Resistance. Frontiers in immunology, 13, 887348. https://doi.org/10.3389/fimmu.2022.887348
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 18-abr-2024