GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE309nnn/GSE309375/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE309375GEOGSEfalseElevated Serum IL-10 in the Setting of Relapsed B-ALL in Patients Previously Treated with CARTCytokine release syndrome (CRS) is a life-threatening toxicity of chimeric antigen receptor T-cell therapy (CART) for B-cell acute lymphoblastic leukemia (B-ALL). Lower rates of severe CRS are reported in patients treated with CD22-directed CART (CART22) compared to those treated with CD19-directed CART (CART19). Here, we identify interleukin-10 (IL-10) as a critical endogenous modulator of CRS and demonstrate that previous treatment with CART is associated with increased serum IL-10 in the setting of subsequent relapse. Mechanistically, IL-10 induced higher interferon gamma (IFNγ) expression and SOCS3 upregulation in both CART19 and CART22 cells. IL-10 differentially impacted the CART immune synapse, prolonging the CART19 but shortening the CART22 immune synapse. Using single cell RNA sequencing (scRNAseq) we demonstrate upregulation of SOCS3 in CART22 patient CD4 T-cells, potentially suppressing gp130-mediated IL-6 signaling. These findings reveal IL-10 as a potent CRS‐mitigating factor and support IL-10 enhancement strategies to improve the safety of CART.2026/07/01GSE309375GSM9266440GSM9266441GSM9266442GSM9266443GSM9266400GSM9266444GSM9266401GSM9266445GSM9266446GSM9266402GSM9266403GSM9266447GSM9266404GSM9266448GSM9266449GSM9266405GSM9266439GSM9266430GSM9266431GSM9266432GSM9266433GSM9266434GSM9266435GSM9266436GSM9266437GSM9266438GSM9266428GSM9266429GSM9266460GSM9266461GSM9266462GSM9266463GSM9266420GSM9266464GSM9266421GSM9266422GSM9266423GSM9266424GSM9266425GSM9266426GSM9266427GSM9266417GSM9266418GSM9266419GSM9266450GSM9266451GSM9266452GSM9266453GSM9266410GSM9266454GSM9266455GSM9266411GSM9266412GSM9266456GSM9266457GSM9266413GSM9266414GSM9266458GSM9266459GSM9266415GSM9266416GSM9266406GSM9266407GSM9266408GSM926640924676309375Homo sapiens[42320984]