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The cellular ratio of immune tolerance (immunoCRIT) is a definite marker for aggressiveness of solid tumors and may explain tumor dissemination patterns

The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to dis...

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Main Authors: Türbachova, Ivana (Author) , Schwachula, Tim (Author) , Vasconcelos, Ines (Author) , Mustea, Alexander (Author) , Baldinger, Tina (Author) , Jones, Katherine A (Author) , Bujard, Hermann (Author) , Olek, Alexander (Author) , Olek, Klaus (Author) , Gellhaus, Katharina (Author) , Braicu, Ioana (Author) , Könsgen, Dominique (Author) , Fryer, Christy (Author) , Ravot, Elisabetta (Author) , Hellwag, Alexander (Author) , Westerfeld, Nicole (Author) , Gruss, Oliver (Author) , Meissner, Markus (Author) , Hasan, Mazahir (Author) , Weber, Michael (Author) , Hoffmüller, Ulrich (Author) , Zimmermann, Sven (Author) , Loddenkemper, Christoph (Author) , Mahner, Sven (Author) , Babel, Nina (Author) , Berns, Els (Author) , Adams, Richard (Author) , Zeilinger, Robert (Author) , Baron, Udo (Author) , Vergote, Ignace (Author) , Maughan, Tim (Author) , Marmé, Frederik (Author) , Dickhaus, Thorsten (Author) , Sehouli, Jalid (Author) , Olek, Sven (Author)
Format: Article (Journal)
Language:English
Published: 26 Sep 2013
In: Epigenetics
Year: 2013, Volume: 8, Issue: 11, Pages: 1226-1235
ISSN:1559-2308
DOI:10.4161/epi.26334
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4161/epi.26334
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Author Notes:Ivana Türbachova, Tim Schwachula, Ines Vasconcelos, Alexander Mustea, Tina Baldinger, Katherine A Jones, Hermann Bujard, Alexander Olek, Klaus Olek, Katharina Gellhaus, Ioana Braicu, Dominique Könsgen, Christy Fryer, Elisabetta Ravot, Alexander Hellwag, Nicole Westerfeld, Oliver J Gruss, Markus Meissner, Mazahir T Hasan, Michael Weber, Ulrich Hoffmüller, Sven Zimmermann, Christoph Loddenkemper, Sven Mahner, Nina Babel, Els Berns, Richard Adams, Robert Zeilinger, Udo Baron, Ignace Vergote, Tim Maughan, Frederik Marme, Thorsten Dickhaus, Jalid Sehouli, and Sven Olek

MARC

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520 |a The adaptive immune system is involved in tumor establishment and aggressiveness. Tumors of the ovaries, an immune-privileged organ, spread via transceolomic routes and rarely to distant organs. This is contrary to tumors of non-immune privileged organs, which often disseminate hematogenously to distant organs. Epigenetics-based immune cell quantification allows direct comparison of the immune status in benign and malignant tissues and in blood. Here, we introduce the “cellular ratio of immune tolerance” (immunoCRIT) as defined by the ratio of regulatory T cells to total T lymphocytes. The immunoCRIT was analyzed on 273 benign tissue samples of colorectal, bronchial, renal and ovarian origin as well as in 808 samples from primary colorectal, bronchial, mammary and ovarian cancers. ImmunoCRIT is strongly increased in all cancerous tissues and gradually augmented strictly dependent on tumor aggressiveness. In peripheral blood of ovarian cancer patients, immunoCRIT incrementally increases from primary diagnosis to disease recurrence, at which distant metastases frequently occur. We postulate that non-pathological immunoCRIT values observed in peripheral blood of immune privileged ovarian tumor patients are sufficient to prevent hematogenous spread at primary diagnosis. Contrarily, non-immune privileged tumors establish high immunoCRIT in an immunological environment equivalent to the bloodstream and thus spread hematogenously to distant organs. In summary, our data suggest that the immunoCRIT is a powerful marker for tumor aggressiveness and disease dissemination. 
650 4 |a epigenetic immunophenotyping 
650 4 |a immunoCRIT 
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650 4 |a regulatory T cells 
650 4 |a T lymphocytes 
650 4 |a tumor immunology 
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