{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328664/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328664"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"PD-1 regulates latent effector differentiation of thymic cytotoxic CD8+ T cells","description":"Durable 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.","dates":{"publication":"2026/05/01"},"accession":"GSE328664","cross_references":{"GSM":["GSM9686914","GSM9686915","GSM9686916","GSM9686917","GSM9686918","GSM9686919","GSM9686886","GSM9686920","GSM9686887","GSM9686921","GSM9686888","GSM9686889","GSM9686922","GSM9686923","GSM9686924","GSM9686903","GSM9686904","GSM9686905","GSM9686906","GSM9686907","GSM9686908","GSM9686909","GSM9686910","GSM9686911","GSM9686912","GSM9686913","GSM9686936","GSM9686937","GSM9686938","GSM9686939","GSM9686940","GSM9686941","GSM9686942","GSM9686943","GSM9686900","GSM9686944","GSM9686901","GSM9686945","GSM9686902","GSM9686925","GSM9686926","GSM9686927","GSM9686928","GSM9686929","GSM9686890","GSM9686891","GSM9686892","GSM9686893","GSM9686894","GSM9686895","GSM9686896","GSM9686897","GSM9686930","GSM9686931","GSM9686898","GSM9686932","GSM9686899","GSM9686933","GSM9686934","GSM9686935"],"GPL":["34281"],"GSE":["328664"],"taxon":["Homo sapiens"]}}