Evidence map›Paper›PMID 39773566›Full record

ArticleJournal for immunotherapy of cancer2025

Chemotherapy-induced cellular senescence promotes stemness of aggressive B-cell non-Hodgkin's lymphoma via CCR7/ARHGAP18/IKBα signaling activation.

Jiyu Wang, Qianshan Tao, Keke Huang, Yangyang Wang, Linhui Hu, Anwen Ren, Huiping Wang, Yang Wan, Jinlan Li, Liuying Yi and 5 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Jiyu Wang *Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Qianshan Tao *Department of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Keke Huang *Department of Internal Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, Guangdong, China.
Yangyang WangDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Linhui HuDepartment of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Anwen RenDepartment 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.
Huiping WangDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Yang WanDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Jinlan LiDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Liuying YiDepartment of Hematology, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Yanjie RuanDepartment of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Zhixiang WanyanDepartment of Emergency, The Third People's Hospital of Hefei, Hefei, Anhui, China.
Fan WuDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
Zhimin ZhaiDepartment of Hematology, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China chaohongliu80@126.com zzzm889@163.com.ORCID http://orcid.org/0000-0003-4060-7600
Chaohong LiuDepartment 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 chaohongliu80@126.com zzzm889@163.com.ORCID http://orcid.org/0000-0001-7028-4625

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundResistance to existing therapies is a major cause of treatment failure in patients with refractory and relapsed B-cell non-Hodgkin's lymphoma (r/r B-NHL). Therapy-induced senescence (TIS) is one of the most important mechanisms of drug resistance.

methodsThis 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 β-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 IKBα and ARHGAP/RhoA inhibition on B-NHL-TIS.

resultsHere 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/IKBα signaling.

conclusionsTogether, TIS promotes the stemness of B-NHL cells via CCR7/ARHGAP18/IKBα signaling activation and targeting CCR7/ARHGAP18 might overcome the chemoresistance of senescent B-NHL cells by inhibiting stemness acquisition and maintenance.

Indexed as

Cellular SenescenceReceptors, CCR7Signal TransductionCell Line, TumorCell ProliferationDoxorubicinFemaleGTPase-Activating ProteinsHumansLymphoma, B-CellMaleMiddle AgedNeoplastic Stem CellsNF-KappaB Inhibitor alphaCCR7 protein, humanDoxorubicinGTPase-Activating ProteinsNF-KappaB Inhibitor alphaReceptors, CCR7B cellChemotherapyCytokineHematologic MalignanciesStem cell

Identifiers

PMID39773566
PMCPMC11749403

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.