{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:10:04Z","timestamp":1793329804572,"version":"4.5.0"},"reference-count":84,"publisher":"American Association for Cancer Research (AACR)","issue":"6","funder":[{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["LLS-SCOR 7012-16"],"award-info":[{"award-number":["LLS-SCOR 7012-16"]}],"id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005189","name":"Leukemia and Lymphoma Society","doi-asserted-by":"publisher","award":["LLS TRP R6510-19"],"award-info":[{"award-number":["LLS TRP R6510-19"]}],"id":[{"id":"10.13039\/100005189","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH NCI","doi-asserted-by":"publisher","award":["R01CA242069"],"award-info":[{"award-number":["R01CA242069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease. Transcriptomic and genetic characterization of DLBCL has increased the understanding of its intrinsic pathogenesis and provided potential therapeutic targets. However, the role of the microenvironment in DLBCL biology remains less understood. Here, we performed a transcriptomic analysis of the microenvironment of 4,655 DLBCLs from multiple independent cohorts and described four major lymphoma microenvironment categories that associate with distinct biological aberrations and clinical behavior. We also found evidence of genetic and epigenetic mechanisms deployed by cancer cells to evade microenvironmental constraints of lymphoma growth, supporting the rationale for implementing DNA hypomethylating agents in selected patients with DLBCL. In addition, our work uncovered new therapeutic vulnerabilities in the biochemical composition of the extracellular matrix that were exploited to decrease DLBCL proliferation in preclinical models. This novel classification provides a road map for the biological characterization and therapeutic exploitation of the DLBCL microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>In a translational relevant transcriptomic-based classification, we characterized the microenvironment as a critical component of the B-cell lymphoma biology and associated it with the DLBCL clinical behavior establishing a novel opportunity for targeting therapies.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 1307<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-20-0839","type":"journal-article","created":{"date-parts":[[2021,2,4]],"date-time":"2021-02-04T12:01:53Z","timestamp":1612440113000},"page":"1468-1489","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":267,"title":["Clinical and Biological Subtypes of B-cell Lymphoma Revealed by Microenvironmental Signatures"],"prefix":"10.1158","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6393-7357","authenticated-orcid":false,"given":"Nikita","family":"Kotlov","sequence":"first","affiliation":[{"name":"1BostonGene Corporation, Waltham, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-854X","authenticated-orcid":false,"given":"Alexander","family":"Bagaev","sequence":"additional","affiliation":[{"name":"1BostonGene Corporation, Waltham, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-0713","authenticated-orcid":false,"given":"Maria V.","family":"Revuelta","sequence":"additional","affiliation":[{"name":"2Hematology and Oncology Division, Medicine Department, New York Presbyterian Hospital, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2999-5254","authenticated-orcid":false,"given":"Jude M.","family":"Phillip","sequence":"additional","affiliation":[{"name":"2Hematology and Oncology Division, Medicine Department, New York Presbyterian Hospital, Weill Cornell Medicine, New York, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Cacciapuoti","sequence":"additional","affiliation":[{"name":"3Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medicine, New York, New 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