{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T23:53:48Z","timestamp":1783727628851,"version":"3.55.0"},"reference-count":42,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"unspecified","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,2,12]]},"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Approximately one-third of diffuse large B cell lymphoma (DLBCL) patients exhibit co-expression of MYC and BCL2 (double-expressor lymphoma, DEL) and have a dismal prognosis. Targeted inhibition of the anti-apoptotic protein BCL2 with venetoclax (ABT-199) has been approved in multiple B-cell malignancies and is currently being investigated in clinical trials for DLBCL. Whether BCL2 anti-apoptotic function represents a multifaceted vulnerability for DEL-DLBCL, affecting both lymphoma B cells and T cells within the tumor microenvironment, remains to be elucidated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here, we present novel genetically engineered mice that preclinically recapitulate DEL-DLBCL lymphomagenesis, and evaluate their sensitivity ex vivo and in vivo to the promising combination of venetoclax with anti-CD20-based standard immunotherapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Venetoclax treatment demonstrated specific killing of MYC<jats:sup>+<\/jats:sup>\/BCL2<jats:sup>+<\/jats:sup> lymphoma cells by licensing their intrinsically primed apoptosis, and showed previously unrecognized immunomodulatory activity by specifically enriching antigen-activated effector CD8 T cells infiltrating the tumors. Whereas DEL-DLBCL mice were refractory to venetoclax alone, inhibition of BCL2 significantly extended overall survival of mice that were simultaneously treated with a murine surrogate for anti-CD20 rituximab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results suggest that the combination of anti-CD20-based immunotherapy and BCL2 inhibition leads to cooperative immunomodulatory effects and improved preclinical responses, which may offer promising therapeutic opportunities for DEL-DLBCL patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-006113","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T10:55:16Z","timestamp":1677581716000},"page":"e006113","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Venetoclax improves CD20 immunotherapy in a mouse model of MYC\/BCL2 double-expressor diffuse large B-cell lymphoma"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct02055820","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03036904","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03984448","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1793-4152","authenticated-orcid":false,"given":"Javier","family":"Melchor","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Genetics, Universidad de Navarra, Pamplona, Spain"},{"name":"Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0614-8682","authenticated-orcid":false,"given":"Marcos","family":"Garcia-Lacarte","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics, Universidad de Navarra, Pamplona, Spain"},{"name":"Hemato-Oncology Program, Center for Applied Medical Research (CIMA), Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-1805","authenticated-orcid":false,"given":"Sara C.","family":"Grijalba","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics, Universidad de Navarra, Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0687-0053","authenticated-orcid":false,"given":"Adri\u00e1n","family":"Arnaiz-Lech\u00e9","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Genetics, Universidad de Navarra, Pamplona, Spain"},{"name":"Navarra Institute for Health Research (IdiSNA), Pamplona, 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