{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T06:16:31Z","timestamp":1778220991511,"version":"3.51.4"},"reference-count":112,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2022MH310, ZR2025QC1700"],"award-info":[{"award-number":["ZR2022MH310, ZR2025QC1700"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma in adults. Although 60\u201370% of patients achieve remission with first-line immunochemotherapy (R-CHOP or pola-R-CHP), approximately 30%-40% of patients still experience develop refractory or relapsed disease. Treatment resistance still remains as the major challenge in DLBCL patient management. Although there is no significant synergy among the components in the R-CHOP or Pola-R-CHP regimens, cross-resistance between these treatments is minimal. Elucidating the mechanisms underlying drug resistance and developing innovative therapeutic strategies are essential for enhancing the clinical outcomes for this patient cohort. This article provides a detailed and up-to-date review of the molecular mechanisms of resistance to the current treatment options in DLBCL. We lastly highlight potential strategies for the rational management of treatment resistance.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1776324","type":"journal-article","created":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T05:50:20Z","timestamp":1778219420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of first-line treatment resistance in diffuse large B-cell lymphoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhumei","family":"Zhan","sequence":"first","affiliation":[{"name":"Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, 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