{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:12:07Z","timestamp":1789567927556,"version":"build-2803163510"},"reference-count":50,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"content-version":"unspecified","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2208085MH217"],"award-info":[{"award-number":["2208085MH217"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370225"],"award-info":[{"award-number":["82370225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2024,11,23]]},"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Resistance to existing therapies is a major cause of treatment failure in patients with refractory and relapsed B-cell non-Hodgkin\u2019s lymphoma (r\/r B-NHL). Therapy-induced senescence (TIS) is one of the most important mechanisms of drug resistance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study used single-cell RNA sequencing to analyze doxorubicin-induced senescent B-NHL cells. C-C chemokine receptor 7 (CCR7) expression in patients with aggressive B-NHL was assessed using immunohistochemistry and flow cytometry. Lentiviral transfection was used to target CCR7 expression in Raji and SU-DHL-2 cells. Protein localization was visualized through immunofluorescence, while western blotting and co-immunoprecipitation were used to analyze protein expression and interactions. Cell proliferation was measured with the Cell Counting Kit-8 assay, and senescent cells were detected using senescence-associated \u03b2-galactosidase staining. The stemness of cells was evaluated through colony and sphere formation assays. Transwell assays assessed cell migration and invasion. Finally, inhibitors GS143 and Y27632 were used to examine the effect of IKB\u03b1 and ARHGAP\/RhoA inhibition on B-NHL-TIS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Here we identified a distinct group of TIS, composed of memory B-cell population characterized by strong positive expression of CCR7, which was significantly elevated in TIS population compared with normal proliferating and autonomously senescent lymphoma cell populations. Additionally, CCR7 expression was significantly upregulated in patients with r\/r B-NHL, and was an independent prognostic factor in B-NHL, with high CCR7 expression being strongly associated with poor prognosis. In vitro results indicated that CCL21 induced migration and invasion of B-NHL cells via CCR7, while blocking CCR7 reduced doxorubicin-induced migration and invasion of these cells. Furthermore, B-NHL-TIS regulated by CCR7 and exhibited enhanced phenotypic and functional stemness features, including the upregulation of stemness markers, increased colony-forming, invasive and migratory capabilities. Mechanistically, blocking CCR7 reversed the stemness characteristics of senescent B-NHL cells by inhibiting the activation of ARHGAP18\/IKB\u03b1 signaling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Together, TIS promotes the stemness of B-NHL cells via CCR7\/ARHGAP18\/IKB\u03b1 signaling activation and targeting CCR7\/ARHGAP18 might overcome the chemoresistance of senescent B-NHL cells by inhibiting stemness acquisition and maintenance.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2024-009356","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T14:21:07Z","timestamp":1736259667000},"page":"e009356","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Chemotherapy-induced cellular senescence promotes stemness of aggressive B-cell non-Hodgkin\u2019s lymphoma via CCR7\/ARHGAP18\/IKB\u03b1 signaling activation"],"prefix":"10.1136","volume":"13","author":[{"given":"Jiyu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China"},{"name":"Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonostic Infectious Disease, Huazhong University of Science and Technology, Wuhan, Hubei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianshan","family":"Tao","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, Guangdong, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liuying","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang, 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