{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T12:19:18Z","timestamp":1780575558734,"version":"3.54.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,10,4]],"date-time":"2020-10-04T00:00:00Z","timestamp":1601769600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002947","name":"Anhui Medical University","doi-asserted-by":"publisher","award":["2018xkj026"],"award-info":[{"award-number":["2018xkj026"]}],"id":[{"id":"10.13039\/501100002947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81670179"],"award-info":[{"award-number":["81670179"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The underlying cause of relapsed and refractory (r\/r) diffuse large B\u2010cell lymphoma (DLBCL) is usually related to apoptosis resistance to antitumor drugs. The recent years have provided lots of evidence that tumor cells may undergo stress\u2010induced premature senescence (SIPS) in response to chemotherapy, but how SIPS affects\u00a0lymphoma cells\u00a0remains inconclusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty\u2010two\u00a0DLBCL patients, including 6 newly diagnosed (ND), 17 complete remissions (CR), and 29 (r\/r), were enrolled in this study. We used a senescence\u2010associated\u2010\u03b2\u2010galactosidase (SA\u2010\u03b2\u2010Gal) staining kit for senescence staining. Suppressive immune cells including regulatory T cells (Treg) and myeloid\u2010derived suppressor cells (MDSC) were detected by flow cytometry (FCM). Secreted cytokines were measured by ELISA Kit and <jats:italic>SENEX<\/jats:italic> gene expression was detected by a quantitative real\u2010time polymerase chain reaction. We used 40\u2009nM doxorubicin to induce the SIPS model of DLBCL in vitro. Apoptosis and proliferation activity of senescent LY8 cells were respectively detected by FCM and CCK8. <jats:italic>SENEX<\/jats:italic> gene was silenced by RNA interference.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The proportion of senescent lymphoma cells was significantly increased in r\/r DLBCL patients, concomitant with increased Treg, MDSC, and various secreted cytokines with proinflammatory and immunosuppressive effects. The\u00a0<jats:italic>SENEX<\/jats:italic> gene was significantly elevated in the SIPS model. Senescent DLBCL cells had good\u00a0antiapoptotic ability and proliferative activity accompanied by increased immunosuppressive cytokines. Interestingly, when we silenced the\u00a0<jats:italic>SENEX<\/jats:italic> gene in the DLBCL cell line, the results were the opposite to the above.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SIPS activated by the\u00a0<jats:italic>SENEX<\/jats:italic> gene mediates apoptosis resistance of r\/r DLBCL via promoting immunosuppressive cells and cytokines.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.356","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T05:22:44Z","timestamp":1601875364000},"page":"672-683","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Stress\u2010induced premature senescence activated by the\u00a0<i>SENEX<\/i> gene mediates apoptosis resistance of diffuse large B\u2010cell lymphoma via promoting immunosuppressive cells and 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