{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:52:34Z","timestamp":1780987954733,"version":"3.54.1"},"reference-count":185,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>As the traditional first-line standard treatment of B-cell non-Hodgkin\u2019s lymphoma, the R-CHOP chemotherapy regimen faces the problem of about 30%-40% of patients progressing into relapsed or refractory disease. Small molecule targeted drugs and CAR-T cell therapy, represented by BTK inhibitors and Bcl-2 inhibitors have achieved breakthrough results in the treatment of lymphoma, but they still face restrictions such as limited single-drug efficacy, drug-resistant recurrence, and toxic reactions. In order to overcome the shortcomings of single therapy, combined treatment strategies have become a research hotspot. This review systematically summarizes the efficacy evidence of the current preclinical and early clinical combined treatment of small molecule targeted drugs and CAR-T cell therapy. The potential synergistic mechanism of the joint application of small molecule targeted drugs and CAR-T cell therapy is discussed, including improving the tumor microenvironment, enhancing the function of CAR-T cells, improving the sensitivity of tumor cells to CAR-T, inhibiting exhaustion, and reducing toxicity. This joint strategy is expected to improve the therapeutic effect and overcome drug resistance. It is a very promising development direction for the treatment of relapsed or refractory lymphoma in the future. At the same time, further in-depth research is needed to promote its clinical transformation and application.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1792910","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:44:09Z","timestamp":1775022249000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas"],"prefix":"10.3389","volume":"17","author":[{"given":"Wenhao","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s40364-017-0102-y","article-title":"Engineering CAR-T cells","volume":"5","author":"Zhang","year":"2017","journal-title":"biomark Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12943-022-01669-8","article-title":"Tumor buster - where will the CAR-T cell therapy \"missile\" go","volume":"21","author":"Qu","year":"2022","journal-title":"Mol 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