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Pulling out the stops: Deletion of regnase-1 promotes anti-tumor activity in NK cells - EurekAlert
Research collaboration between Osaka University and Otsuka Pharmaceutical Co., Ltd. revealed that deletion of mRNA endonuclease Regnase-1 promoted NK cell anti-tumor activity via OCT2-dependent transcriptional up-regulation of Ifng mRNA. Associated with the deletion of Regnase-1 in NK cells, NK cells showed a high expression of OCT2 and CXCR6 in those that escaped from mRNA decay from Regnase-1, and they contributed to the transcriptional regulation of Ifng and NK cell persistence inside the tumor microenvironment, respectively. The loss-of-function strategy targeting Regnase-1 potentially enhances the production of cytotoxic proteins such as IFN-γ, granzymes, and perforin. This approach also promotes NK cell infiltration and persistence within the tumor, thereby facilitating the development of effective anti-tumor immunotherapy against solid tumors.
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