Nature 576, 471–476 (2019)
Activated T cells often become less functional in the tumor microenvironment or during chronic infection. In Nature, Chi and colleagues describe an unbiased CRISPR-Cas9 screen in CD8+ T cells that identifies Regnase-1 as a negative regulator of T cell function within the tumor environment. Regnase-1-null CD8+ T cells persist longer in tumors, exhibit enhanced mitochondrial spare respiratory capacity and increased oxidative phosphorylation, and express more effector molecules as compared to wild-type cells. Tumor-bearing mice receiving Regnase-1-null CD8+ T cells also survive longer. The authors also identify mRNAs encoding the transcription factor BATF as a major target of Regnase-1, as deletion of Batf abolished the enhanced antitumor activity of Regnase-1-null CD8+ T cells. These findings reveal Regnase-1 as a regulator of cytotoxic T cell function within the tumor microenvironment.
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Dempsey, L.A. Regnase-1 in the TME. Nat Immunol 21, 103 (2020). https://doi.org/10.1038/s41590-020-0591-y
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DOI: https://doi.org/10.1038/s41590-020-0591-y