{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T13:50:34Z","timestamp":1781877034353,"version":"3.54.5"},"reference-count":36,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"unspecified","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000884","name":"Cancer Research Institute","doi-asserted-by":"publisher","award":["CRI12698"],"award-info":[{"award-number":["CRI12698"]}],"id":[{"id":"10.13039\/100000884","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["K08CA277013"],"award-info":[{"award-number":["K08CA277013"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["K08CA286762"],"award-info":[{"award-number":["K08CA286762"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031022","name":"Center for Cancer Research","doi-asserted-by":"publisher","award":["P01 CA214278"],"award-info":[{"award-number":["P01 CA214278"]}],"id":[{"id":"10.13039\/100031022","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI147118"],"award-info":[{"award-number":["R01AI147118"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leukemia & Lymphoma Society","award":["NA"],"award-info":[{"award-number":["NA"]}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute for Health Research","doi-asserted-by":"crossref","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001445","name":"Alex\u2019s Lemonade Stand Foundation for Childhood Cancer","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100001445","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,5,21]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cytokine 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 have been reported in patients treated with CD22-directed CART (CART22) compared with those treated with CD19-directed CART (CART19).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>More than 1,000 serum proteins were measured using a proximity extension assay on 40 patients treated with CART19 or CART22 and cytokines were compared. Single-cell (single-cell RNA-sequencing (scRNAseq)) was used to identify cellular and transcriptional differences between patients treated with CART19 and CART22. CART19-blast and CART22-blast interactions at the immune synapse (IS) were modeled in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified interleukin-10 (IL-10) as a critical endogenous modulator of CRS and demonstrated 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 expression and\n                      <jats:italic>SOCS3<\/jats:italic>\n                      upregulation in both CART19 and CART22 cells. IL-10 differentially impacted the CART IS, prolonging the CART19 but shortening the CART22 IS. Using scRNAseq we demonstrated upregulation of\n                      <jats:italic>SOCS3<\/jats:italic>\n                      in CART22 patient CD4 T-cells, potentially suppressing trans-IL-6 signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings reveal IL-10 as a potent CRS\u2010mitigating factor and support IL-10 enhancement strategies to improve the safety of CART.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015126","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T12:50:36Z","timestamp":1781873436000},"page":"e015126","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Differential cytokine architecture in patients treated with CART19 versus 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