{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:08:49Z","timestamp":1790770129438,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,6,8]],"date-time":"2009-06-08T00:00:00Z","timestamp":1244419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rituximab (RTX), a chimeric anti\u2010CD20 antibody, is associated with direct induction of apoptosis and antibody\u2010dependent cell\u2010mediated cytotoxicity (ADCC) with clinical efficacy in mantle cell lymphoma (MCL). Lenalidomide (LEN), a novel immunomodulatory agent, sensitizes tumor cells and enhances ADCC. Our study attempted to elucidate the mechanism of LEN\u2010enhanced RTX\u2010mediated cytotoxicity of MCL cells. We found that LEN and RTX induced growth inhibition of both cultured and fresh primary MCL cells. LEN enhanced RTX\u2010induced apoptosis via upregulating phosphorylation of c\u2010Jun N\u2010terminal protein kinases (JNK), Bcl\u20102, Bad; increasing release of cytochrome\u2010c; enhancing activation of caspase\u20103, \u20108, \u20109 and cleavage of PARP. Meanwhile, LEN activated NK cells and increased CD16 expression on CD56<jats:sup>low<\/jats:sup>CD16<jats:sup>+<\/jats:sup> NK cells. Whole PBMCs but not NK cell\u2010depleted PBMCs treated with LEN augmented 30% of RTX\u2010dependent cytotoxicity. Daily treatment with LEN increased NK cells by 10\u2010folds in SCID mice, and combination of LEN and RTX decreased tumor burden and prolonged survival of MCL\u2010bearing SCID mice. Taken together, our study demonstrates that LEN plus RTX provides a synergistically therapeutic effect on MCL cells by enhancing apoptosis and RTX\u2010dependent NK cell\u2010mediated cytotoxicity and may be an optimal combination in the clinical trial of relapsed or refractory MCL. Am. J. Hematol. 2009. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.21468","type":"journal-article","created":{"date-parts":[[2009,6,8]],"date-time":"2009-06-08T17:45:52Z","timestamp":1244483152000},"page":"553-559","source":"Crossref","is-referenced-by-count":127,"title":["Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo"],"prefix":"10.1002","volume":"84","author":[{"given":"Liang","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengzi","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luhong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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