{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T14:02:21Z","timestamp":1774015341371,"version":"3.50.1"},"posted":{"date-parts":[[2026,3,18]]},"group-title":"Oncology","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,18]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy can induce durable remissions in patients with large B-cell lymphoma (LBCL), yet outcomes remain variable. Reliable pre-treatment predictors of durable response remain limited, leaving a critical gap in patient management. To address this, we profiled pre-treatment plasma cell-free RNA (cfRNA) from 91 LBCL patients treated with axicabtagene ciloleucel (axi-cel, Yescarta) across three independent cohorts. We first demonstrated that signatures of \u201clymph node-like\u201d tumor microenvironments (TMEs), previously identified in tumor biopsies and shown to correlate with favorable outcomes, are specifically elevated in the pre-treatment plasma cfRNA of responders, but not in matched peripheral blood mononuclear cells (PBMCs). These observations indicate that cfRNA captures TME tissue-derived signals not reflected in circulating immune cells. Next, using unbiased approaches, we identified additional cfRNA signatures associated with one-year clinical outcomes that capture the underlying biological landscape of treatment response. Collectively, these findings support pre-treatment plasma cfRNA as a minimally invasive surrogate of TME state to prospectively inform durable CAR T-cell therapy outcomes and guide risk stratification and TME-modulating adjunct therapies.<\/jats:p>","DOI":"10.64898\/2026.03.16.26348550","type":"posted-content","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T22:35:27Z","timestamp":1773873327000},"source":"Crossref","is-referenced-by-count":0,"title":["Cell-free RNA Signatures Derived from the Tumor Microenvironment Predict Outcomes of CAR-T Therapy in Large B Cell Lymphoma"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8816-4293","authenticated-orcid":false,"given":"Conor","family":"Loy","sequence":"first","affiliation":[{"name":"Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glory","family":"Agun","sequence":"additional","affiliation":[{"name":"Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-181X","authenticated-orcid":false,"given":"Katie","family":"Maurer","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA"},{"name":"Department of Medicine, Harvard Medical School; Boston, 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Bosch","family":"Vilaseca","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA"},{"name":"Department of Medicine, Harvard Medical School; Boston, 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Potapova","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caron A.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA"},{"name":"Department of Medicine, Harvard Medical School; Boston, 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jerome","family":"Ritz","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute; Boston, 02215, USA"},{"name":"Department of Medicine, Harvard Medical School; Boston, 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwijn","family":"De Vlaminck","sequence":"additional","affiliation":[{"name":"Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University; Ithaca, 14850, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026032004501076000_2026.03.16.26348550v1.1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022018893"},{"key":"2026032004501076000_2026.03.16.26348550v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.05.026"},{"key":"2026032004501076000_2026.03.16.26348550v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2025.06.002"},{"key":"2026032004501076000_2026.03.16.26348550v1.4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2025017873"},{"key":"2026032004501076000_2026.03.16.26348550v1.5","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020002394"},{"key":"2026032004501076000_2026.03.16.26348550v1.6","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-24-2267"},{"key":"2026032004501076000_2026.03.16.26348550v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01109"},{"key":"2026032004501076000_2026.03.16.26348550v1.8","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.14103"},{"key":"2026032004501076000_2026.03.16.26348550v1.9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2023-180819"},{"key":"2026032004501076000_2026.03.16.26348550v1.10","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-bioeng-110222-111259"},{"key":"2026032004501076000_2026.03.16.26348550v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-22444-1"},{"key":"2026032004501076000_2026.03.16.26348550v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-15843-7"},{"key":"2026032004501076000_2026.03.16.26348550v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101034"},{"key":"2026032004501076000_2026.03.16.26348550v1.14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49245-6"},{"key":"2026032004501076000_2026.03.16.26348550v1.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2403897121"},{"key":"2026032004501076000_2026.03.16.26348550v1.16","unstructured":"The Tabula Sapiens: A multiple-organ, single-cell transcriptomic atlas of humans | Science [Internet]. [cited 2025 Mar 10]. Available from: https:\/\/www.science.org\/doi\/10.1126\/science.abl4896"},{"key":"2026032004501076000_2026.03.16.26348550v1.17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27232-5"},{"key":"2026032004501076000_2026.03.16.26348550v1.18","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abh1873"},{"key":"2026032004501076000_2026.03.16.26348550v1.19","doi-asserted-by":"publisher","DOI":"10.1186\/s13062-025-00694-z"},{"key":"2026032004501076000_2026.03.16.26348550v1.20","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2026032004501076000_2026.03.16.26348550v1.21","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.24656"},{"key":"2026032004501076000_2026.03.16.26348550v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1604780113"},{"key":"2026032004501076000_2026.03.16.26348550v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.13"},{"key":"2026032004501076000_2026.03.16.26348550v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/imr.70062"},{"key":"2026032004501076000_2026.03.16.26348550v1.25","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-3016"},{"key":"2026032004501076000_2026.03.16.26348550v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2023.02.016"},{"key":"2026032004501076000_2026.03.16.26348550v1.27","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101764"},{"key":"2026032004501076000_2026.03.16.26348550v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0667-0"},{"key":"2026032004501076000_2026.03.16.26348550v1.29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1623436"},{"key":"2026032004501076000_2026.03.16.26348550v1.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-08211-w"},{"key":"2026032004501076000_2026.03.16.26348550v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04186-5"},{"key":"2026032004501076000_2026.03.16.26348550v1.32","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts480"},{"key":"2026032004501076000_2026.03.16.26348550v1.33","unstructured":"SourceForge [Internet]. 2023 [cited 2024 Jan 30]. BBMap. Available from: https:\/\/sourceforge.net\/projects\/bbmap\/"},{"key":"2026032004501076000_2026.03.16.26348550v1.34","doi-asserted-by":"publisher","DOI":"10.1101\/gr.209601.116"},{"key":"2026032004501076000_2026.03.16.26348550v1.35","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt656"},{"key":"2026032004501076000_2026.03.16.26348550v1.36","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts503"},{"key":"2026032004501076000_2026.03.16.26348550v1.37","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"2026032004501076000_2026.03.16.26348550v1.38","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"2026032004501076000_2026.03.16.26348550v1.39","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"2026032004501076000_2026.03.16.26348550v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2010.04.018"},{"key":"2026032004501076000_2026.03.16.26348550v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2649-2"},{"key":"2026032004501076000_2026.03.16.26348550v1.42","doi-asserted-by":"publisher","DOI":"10.25080\/Majora-92bf1922-00a"},{"key":"2026032004501076000_2026.03.16.26348550v1.43","unstructured":"GENCODE - Human Release 38 [Internet]. [cited 2026 Feb 24]. Available from: https:\/\/www.gencodegenes.org\/human\/release_38.html"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.03.16.26348550","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T11:50:21Z","timestamp":1774007421000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.03.16.26348550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":43,"URL":"https:\/\/doi.org\/10.64898\/2026.03.16.26348550","relation":{},"subject":[],"published":{"date-parts":[[2026,3,18]]},"subtype":"preprint"}}