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Title: The cellular ratio of immune tolerance (immunoCRIT) is a definite marker for aggressiveness of solid tumors and may explain tumor dissemination patterns
Authors: Türbachova, Ivana ×
Schwachula, Tim
Vasconcelos, Ines
Mustea, Alexander
Baldinger, Tina
Jones, Katherine A
Bujard, Hermann
Olek, Alexander
Olek, Klaus
Gellhaus, Katharina
Braicu, Ioana
Könsgen, Dominique
Fryer, Christy
Ravot, Elisabetta
Hellwag, Alexander
Westerfeld, Nicole
Gruss, Oliver J
Meissner, Markus
Hassan, Mazahir
Weber, Michael
Hoffmüller, Ulrich
Zimmermann, Sven
Loddenkemper, Christoph
Mahner, Sven
Babel, Nina
Berns, Els
Adams, Richard
Zeilinger, Robert
Baron, Udo
Vergote, Ignace
Maughan, Tim
Marme, Frederik
Dickhaus, Thorsten
Sehouli, Jalid
Olek, Sven #
Issue Date: Nov-2013
Publisher: Landes Bioscience
Series Title: Epigenetics vol:8 issue:11 pages:1226-35
Abstract: 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.
ISSN: 1559-2294
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gynaecological Oncology
× corresponding author
# (joint) last author

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