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@ARTICLE{Engels:301476,
      author       = {P. Engels and A. Szolek and S. Hörner$^*$ and G. V.
                      Syrigos and K. Hebbel and M. Schmidtke and M. Zhou and M.
                      Mateo-Tortola and C. Schönfeld and S. Stefanczyk$^*$ and K.
                      Wolter$^*$ and S. Babaei and M. Schindler and M. Claassen
                      and D. Dauch$^*$ and L. Zender$^*$ and A. Tapía-Abellán
                      and A. Weber$^*$},
      title        = {{A}ctionable heterogeneity of hepatocellular carcinoma
                      therapy-induced senescence.},
      journal      = {Cancer immunology immunotherapy},
      volume       = {74},
      number       = {7},
      issn         = {0340-7004},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2025-01018},
      pages        = {207},
      year         = {2025},
      abstract     = {Therapy-induced senescence (TIS) is a stable cell cycle
                      arrest in cancerous cells favoring immune control upon
                      immune cell recruitment and activation via a
                      senescence-associated secretory phenotype (SASP). Numerous
                      studies have investigated the therapeutic applicability of
                      TIS in hepatocellular carcinoma (HCC), a frequent cancer
                      with high morbidity and mortality. Despite these efforts, a
                      comprehensive understanding of how TIS may expose
                      vulnerabilities specifically for immunotherapies, a potent
                      means of cancer therapy, in HCC remains incomplete.
                      Therefore, we conducted systematic studies to carefully
                      characterize actionable and shared SASP- or other
                      senescence-associated molecular parameters of TIS. We
                      systematically compared the TIS inducers, etoposide and
                      alisertib with a novel TIS inducer, CX5461, for their
                      effects on SASP, surfaceome and innate immune clearance of
                      representative human HCC cell lines. Surprisingly, all three
                      compounds induced both metastasis surface antigens but also
                      immunotherapeutically tractable antigens like CD95 (Fas),
                      CD276 (B7-H3) and CD340 (Her2). This was verified in four
                      representative HCC cell lines and publicly available
                      datasets of HCC. Interestingly, alisertib, etoposide and
                      CX5461 rendered senescent HCC vulnerable to be targeted by
                      either T-cell-engaging bispecific antibodies or CAR NK
                      cells. Collectively, our study indicates that heterogenous,
                      but selective features of HCC senescence may be exploited by
                      different immunotherapeutic approaches.},
      keywords     = {Humans / Carcinoma, Hepatocellular: pathology / Carcinoma,
                      Hepatocellular: immunology / Carcinoma, Hepatocellular: drug
                      therapy / Carcinoma, Hepatocellular: therapy / Liver
                      Neoplasms: pathology / Liver Neoplasms: immunology / Liver
                      Neoplasms: drug therapy / Liver Neoplasms: therapy /
                      Cellular Senescence: drug effects / Pyrimidines:
                      pharmacology / Cell Line, Tumor / Etoposide: pharmacology /
                      Azepines: pharmacology / Senescence-Associated Secretory
                      Phenotype: drug effects / Immunotherapy: methods /
                      Hepatocellular carcinoma (Other) / Immunology (Other) /
                      Immunotherapy (Other) / Senescence (Other) / Pyrimidines
                      (NLM Chemicals) / MLN 8237 (NLM Chemicals) / Etoposide (NLM
                      Chemicals) / Azepines (NLM Chemicals)},
      cin          = {TU01},
      ddc          = {610},
      cid          = {I:(DE-He78)TU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40374812},
      pmc          = {pmc:PMC12081809},
      doi          = {10.1007/s00262-025-04060-w},
      url          = {https://inrepo02.dkfz.de/record/301476},
}