GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328664/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328664GEOGSEfalsePD-1 regulates latent effector differentiation of thymic cytotoxic CD8+ T cellsDurable T cell immunity against cancer depends on the continual replenishment of effector CD8⁺ T cells. Thymic output has been associated with favorable prognosis in cancer patients across a range of ages, suggesting that the thymus is an important source for replenishing T cells capable of controlling cancer progression. However, whether CD8⁺ T cells acquire effector potential within the thymus, and how thymic output of effector CD8⁺ T cells contribute to peripheral tumor immunity, remain unclear. In this study, we discover that thymic single-positive (SP) CD8⁺ T cells undergo latent effector differentiation following thymic selection, but this process is subject to PD-1 regulation. We further demonstrate that PD-1 limits the contribution of thymic output of CD8⁺ T cells in shaping the TCR repertoire within the tumor tissues for tumor immunosurveillance. Although PD-1 inhibition facilitates the expansion of effector CD8⁺ T cells in the periphery, these cells gradually lose antitumor activity within tumors due to accelerated exhaustion in the absence of PD-1. Thus, while latent effector differentiation of thymic CD8⁺ T cells enable a rapid response to malignant cells in the periphery, PD-1 restrains this process to prevent overt or terminal effector differentiation, which could compromise balanced and durable peripheral immunity.2026/05/01GSE328664GSM9686914GSM9686915GSM9686916GSM9686917GSM9686918GSM9686919GSM9686886GSM9686920GSM9686887GSM9686921GSM9686888GSM9686889GSM9686922GSM9686923GSM9686924GSM9686903GSM9686904GSM9686905GSM9686906GSM9686907GSM9686908GSM9686909GSM9686910GSM9686911GSM9686912GSM9686913GSM9686936GSM9686937GSM9686938GSM9686939GSM9686940GSM9686941GSM9686942GSM9686943GSM9686900GSM9686944GSM9686901GSM9686945GSM9686902GSM9686925GSM9686926GSM9686927GSM9686928GSM9686929GSM9686890GSM9686891GSM9686892GSM9686893GSM9686894GSM9686895GSM9686896GSM9686897GSM9686930GSM9686931GSM9686898GSM9686932GSM9686899GSM9686933GSM9686934GSM968693534281328664Homo sapiens