Research ArticleCancer

The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy

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Science Translational Medicine  11 Apr 2018:
Vol. 10, Issue 436, eaan3464
DOI: 10.1126/scitranslmed.aan3464

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  • Surgical removal of primary tumors fosters distant metastasis
    • Fedor Donenko, Lab head, Professor, N.N. Blokhin National Medical Research Center of Oncology
    • Other Contributors:
      • Mikail Kiselewskii, Head of Department, Professor, N.N. Blokhin National Medical Research Center of Oncology
      • Thomas Efferth, Head of Department, Professor, Dept. of Pharm. Biology, Johannes Gutenberg Univ. Mainz, Germany

    Krall et al. published an article in your journal about the role of T-cells in the development of recurrent tumors after removal of the primary node (1). Despite the thoroughness of the study, the article raises, but does not answer, at least, three main questions: 1. How do tumor cells and T-cells "recognize" that the primary node is removed? Are there special signals? 2. Is a signal necessary for the growth of recurrent tumor cells after tumor removal? Tumor relapse cannot take place without switch off of this signal. 3. Why has this signal still not been identified? The identification of such a signal is of utmost importance, not only for tumor diagnosis but for therapy as potential antitumor drug.

    We also studied the phenomenon of tumor relapse after removal of the primary node (2-6). Therefore, we want to offer our own explanation of this phenomenon. Firstly, we noted that this phenomenon is specific. If animals were transplanted with two different tumors and only one of them was subsequently removed, recurring tumors appear at remote locations. Secondly, this phenomenon develops rapidly. We removed ascitic Ehrlich carcinoma cells by extraction of ascitic fluid from the abdominal cavity by syringe. During this procedure there was no bleeding or surgical trauma. There was not even contact inhibition of tumor cells in the ascitic fluid. However, only one hour after this procedure, we noticed a changed morphology of non-removed remaining ascitic cells. T...

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    Competing Interests: None declared.
  • RE: Comment on ‘The systemic response to surgery triggers the outgrowth of distant immune-controlled tumors in mouse models of dormancy’
    • Joe Masters, Clinical research fellow, Imperial College London
    • Other Contributors:
      • Daqing Ma Ma, Professor of Anaesthesia and BOC Chair, Imperial College London

    Dear editor – We read the recent article by Krall et al with great interest and thank them for such an elegantly designed study addressing the issue of metastatic recurrence in cancer surgery patients (1). We congratulate the authors for their important findings which have a great translational value. We would however like to invite them to comment on potential factors in their experiments that may be affecting the data.

    For many years, it has been the belief that anaesthetics exert a reversible effect on the central nervous system (CNS) which is returned to a pristine state once the agent is eliminated from the body. However, there is increasing evidence to suggest that anaesthetics exert long lasting biological effects on the whole body due to strongly induced cellular signalling changes in the perioperative period beyond their primary effect of anaesthesia and analgesia (2). Indeed, particularly relevant to this current study, it has been demonstrated that isoflurane (the volatile agent used by the investigators to anesthetise the mice undergoing surgery) exerts a number of tumour-promoting effects in a range of human cancer cells lines (e.g. renal [RCC4] (3), ovarian [SKOV3] (4, 5), and prostate [PC3] (6)) in a dose- and time-dependent manner. These include increased cancer cell proliferation, cytoskeletal rearrangement, upregulation of pro-metastatic mediators (e.g. vascular endothelial growth factor A [VEGF-A], matrix metalloproteinase 11 [MMP11], transformin...

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    Competing Interests: None declared.