{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T13:42:26Z","timestamp":1792071746564,"version":"4.4.0"},"reference-count":73,"publisher":"American Society of Hematology","issue":"21","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,22]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>Most patients with diffuse large B-cell lymphoma (DLBCL) treated with immunotherapies such as bispecific antibodies (BsAbs) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative multiomics approach was applied to multiple large independent data sets to characterize DLBCL immune environments and to define their association with tumor cell\u2013intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 \u00d7 CD3 BsAb therapies. This approach effectively segregated DLBCLs into 4 immune quadrants (IQs) defined by cell-of-origin and immune-related gene set expression scores. These quadrants consisted of activated B cell\u2013like (ABC) hot, ABC cold, germinal center B cell\u2013like (GCB) hot, and GCB cold DLBCLs. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute significantly to orchestrating unique DLBCL immune environments. For instance, SOCS1 loss-of-function mutations were significantly enriched among GCB hot DLBCLs, identifying a putative subset of inflamed DLBCLs that may be inherently susceptible to immunotherapy. In patients with relapsed\/refractory DLBCL, DLBCL-IQ assignment correlated significantly with clinical benefit with a CD20 \u00d7 CD3 BsAb (N = 74), but not with CD19-directed CAR T cells (Stanford, N = 51; Memorial Sloan Kettering Cancer Center, N = 69). Thus, DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and suggests the endogenous immune environment has a more significant impact on outcomes to BsAb than CAR T-cell treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024025355","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T15:59:19Z","timestamp":1737993559000},"page":"2460-2472","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":29,"title":["Integrative genomic analysis of DLBCL identifies immune environments associated with bispecific antibody response"],"prefix":"10.1182","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2091-821X","authenticated-orcid":false,"given":"Sravya","family":"Tumuluru","sequence":"first","affiliation":[{"name":"1Biological Sciences Division, Committee on Cancer Biology, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4103-4288","authenticated-orcid":false,"given":"James K.","family":"Godfrey","sequence":"additional","affiliation":[{"name":"2Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-0866","authenticated-orcid":false,"given":"Alan","family":"Cooper","sequence":"additional","affiliation":[{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9214-7576","authenticated-orcid":false,"given":"Jovian","family":"Yu","sequence":"additional","affiliation":[{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufen","family":"Chen","sequence":"additional","affiliation":[{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1827-0247","authenticated-orcid":false,"given":"Brendan W.","family":"MacNabb","sequence":"additional","affiliation":[{"name":"4Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"5Department of Pathology, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zha","sequence":"additional","affiliation":[{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1892-3650","authenticated-orcid":false,"given":"Benedikt","family":"Pelzer","sequence":"additional","affiliation":[{"name":"6Department of Medicine, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo","family":"Song","sequence":"additional","affiliation":[{"name":"7Department of Pathology, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerben","family":"Duns","sequence":"additional","affiliation":[{"name":"8Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-5507","authenticated-orcid":false,"given":"Brian J.","family":"Sworder","sequence":"additional","affiliation":[{"name":"9Division of Hematology\/Oncology, Department of Medicine, University of California, Irvine, Irvine, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-0528","authenticated-orcid":false,"given":"Sandeep","family":"Raj","sequence":"additional","affiliation":[{"name":"10Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Bolen","sequence":"additional","affiliation":[{"name":"11Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elicia","family":"Penuel","sequence":"additional","affiliation":[{"name":"11Genentech Inc, South San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3413-3122","authenticated-orcid":false,"given":"Ekaterina","family":"Postovalova","sequence":"additional","affiliation":[{"name":"12BostonGene Corporation, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6393-7357","authenticated-orcid":false,"given":"Nikita","family":"Kotlov","sequence":"additional","affiliation":[{"name":"12BostonGene Corporation, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-854X","authenticated-orcid":false,"given":"Aleksander","family":"Bagaev","sequence":"additional","affiliation":[{"name":"12BostonGene Corporation, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Fowler","sequence":"additional","affiliation":[{"name":"12BostonGene Corporation, Waltham, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-8032","authenticated-orcid":false,"given":"Roni","family":"Shouval","sequence":"additional","affiliation":[{"name":"6Department of Medicine, Weill Cornell Medical College, New York, NY"},{"name":"10Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9893-4949","authenticated-orcid":false,"given":"Sonali M.","family":"Smith","sequence":"additional","affiliation":[{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5153-5625","authenticated-orcid":false,"given":"Ash A.","family":"Alizadeh","sequence":"additional","affiliation":[{"name":"13Division of Oncology, Department of Medicine, Stanford University, Palo Alto, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9842-9750","authenticated-orcid":false,"given":"Christian","family":"Steidl","sequence":"additional","affiliation":[{"name":"8Centre for Lymphoid Cancer, British Columbia Cancer, Vancouver, BC, Canada"},{"name":"14Department of Pathology and Laboratory Medicine, The University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Kline","sequence":"additional","affiliation":[{"name":"1Biological Sciences Division, Committee on Cancer Biology, The University of Chicago, Chicago, IL"},{"name":"3Section of Hematology\/Oncology, Department of Medicine, The University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"26","key":"2025060309060747300_bib1","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1056\/NEJMoa1707447","article-title":"Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma","volume":"377","author":"Neelapu","year":"2017","journal-title":"N Engl J 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