{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE326nnn/GSE326883/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE326883"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"TLR9 Agonists Potentiate Adoptive T Cell Therapy in Cancer through a B Cell–CD2 Costimulatory Axis","description":"Adoptive T cell transfer (ACT) therapy offers curative potential for some patients with cancer. Toll-like receptor (TLR) agonists improve the efficacy of ACT therapy, but the underlying mechanism of potency remains poorly understood. Here, we identify a previously unrecognized innate-adaptive circuit in which TLR9-activated B cells augment CD8 T cell fitness and antitumor activity through CD2-dependent costimulation. Among multiple TLR agonist tested, class B CpG uniquely programmed murine and human CD8⁺ T cells for superior effector differentiation, metabolic fitness and antitumor control. Disruption of CD2 signaling blunts the benefits of TLR9 agonism, including glycolytic capacity and tumor control. Independently, blocking CD86/CD80/CD28 or ICOS did not impair CpG conditioned CD8 T cell anti-tumor activity. Gain of function experiments revealed that CD2 stimulation recapitulated the effect of TLR9 agonism, bolstering the effector function of TIL and CAR T cells. Clinically, consistent with these findings, elevated CD2 expression in human tumors correlated with improved overall survival across multiple cancer cohorts, underscoring the importance of this signaling cue. Together, these data uncover a non-canonical B cell-CD2 costimulation axis through which TLR9 agonists potentiate ACT, revealing a targetable pathway to overcome resistance to cell therapy in solid tumors.","dates":{"publication":"2026/04/07"},"accession":"GSE326883","cross_references":{"GSM":["GSM9642056","GSM9642055","GSM9642047","GSM9642057","GSM9642052","GSM9642051","GSM9642054","GSM9642053","GSM9642050","GSM9642049","GSM9642048"],"GPL":["34290"],"GSE":["326883"],"taxon":["Mus musculus"]}}