2026-04-26T22:08:12Zhttps://uvadoc.uva.es/oai/request
oai:uvadoc.uva.es:10324/551542022-09-16T19:00:18Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
UVaDOC author Herrero Sánchez, María del Carmen author Rodríguez Serrano, Concepción author Almeida Parra, Julia author San Segundo Payo, Laura author Inogés Sancho, Laura author Santos-Briz Terrón, Ángel author García Briñón, Jesús author Corchete Sánchez, Luis Antonio author San Miguel Izquierdo, Jesús F. author Cañizo Fernández-Roldán, Consuelo del author Blanco Durango, Belén 2022-09-16T08:39:41Z 2022-09-16T08:39:41Z 2016 Journal of Hematology & Oncology, 2016, Vol. 9, Nº. 113, 15 pp. 1756-8722 https://uvadoc.uva.es/handle/10324/55154 10.1186/s13045-016-0343-5 1 1 15 Journal of Hematology & Oncology 9 1756-8722 Background: Graft-versus-host disease (GvHD) remains the major obstacle to successful allogeneic hematopoietic stem cell transplantation, despite of the immunosuppressive regimens administered to control T cell alloreactivity. PI3K/AKT/mTOR pathway is crucial in T cell activation and function and, therefore, represents an attractive therapeutic target to prevent GvHD development. Recently, numerous PI3K inhibitors have been developed for cancer therapy. However, few studies have explored their immunosuppressive effect. Methods: The effects of a selective PI3K inhibitor (BKM120) and a dual PI3K/mTOR inhibitor (BEZ235) on human T cell proliferation, expression of activation-related molecules, and phosphorylation of PI3K/AKT/mTOR pathway proteins were analyzed. Besides, the ability of BEZ235 to prevent GvHD development in mice was evaluated. Results: Simultaneous inhibition of PI3K and mTOR was efficient at lower concentrations than PI3K specific targeting. Importantly, BEZ235 prevented naïve T cell activation and induced tolerance of alloreactive T cells, while maintaining an adequate response against cytomegalovirus, more efficiently than BKM120. Finally, BEZ235 treatment significantly improved the survival and decreased the GvHD development in mice. Conclusions: These results support the use of PI3K inhibitors to control T cell responses and show the potential utility of the dual PI3K/mTOR inhibitor BEZ235 in GvHD prophylaxis. eng Attribution-NonCommercial-NoDerivatives 4.0 Internacional Cell transplantation Trasplante de células Graft versus host disease Immunology Cell Biology Targeting of PI3K/AKT/mTOR pathway to inhibit T cell activation and prevent graft-versus-host disease development info:eu-repo/semantics/article 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URL https://uvadoc.uva.es/bitstream/10324/55154/1/Targeting-of-PI3KAKTmTOR-pathway-to-inhibit-T-cell.pdf File MD5 2c24c01445d7cfa84431088dff844256 1563383 application/pdf Targeting-of-PI3KAKTmTOR-pathway-to-inhibit-T-cell.pdf