ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR316/069/SRR31643169/SRR31643169_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR316/070/SRR31643170/SRR31643170_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR316/069/SRR31643169/SRR31643169_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR316/070/SRR31643170/SRR31643170_2.fastq.gzprimaryOK200Genomicsschool of medicine, Zhejiang universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1195603Mus musculusxref:PubMed:39759159Protein phosphatase 2A (PP2A) is one of the most abundant serine/threonine phosphatases and plays critical roles in regulating cell fate and function. We previously showed that PP2A regulates the differentiation of CD4+ T cells and the development of thymocytes. Nevertheless, its role in CD8+ T cells remains elusive. By ablating the catalytic subunit α (Cα) of PP2A in CD8+ T cells, we revealed the essential role of PP2A in promoting the effector functions of CD8+ T cells. Notably, PP2A Cα-deficient CD8+ T cells exhibit reduced proliferation and decreased cytokine production upon stimulation in vitro. In vivo, mice lacking PP2A Cα in T cells displayed defective immune responses against lymphocytic choriomeningitis virus infection, associated with reduced CD8+ T cell expansion and decreased cytokine production. Consistently, the ablation of the PP2A Cα subunit in CD8+ T cells results in attenuated antitumor activity in mice. There is a notable decrease in the infiltration of PP2A Cα-deficient CD8+ T cells within the tumor microenvironment, and the cells that do infiltrate exhibit diminished effector functions. Mechanistically, PP2A Cα deficiency impedes CD28-induced AKT Ser473 phosphorylation, thus impairing CD8+ T cell costimulation signal. Collectively, our findings underscore the critical role of phosphatase PP2A as a propeller for CD28-mediated costimulation signaling in CD8+ T cell effector function by fine-tuning T cell activation. Overall design: To inveatigate the role of PP2A in CD8+ T cell effector function, we isolated CD8+ TILs from WT and PP2A cKO tumor bearing mice. Then we performed gene expression profiling analysis using data obtained from scRNA-seq of WT and PP2A cKO CD8+ T cells.ENAfalseEffect of PP2A deficiency on gene expression in CD8+ T cells activation [scRNA-Seq]Effect of PP2A deficiency on gene expression in CD8+ T cells activation [scRNA-Seq]2025-09-242024-12-16PRJNA1195603GSE2838061009039759159