Immune escape of AKT overexpressing ovarian cancer cells

Hahne, Jens C. and Meyer, Susanne R. and Gambaryan, Stepan and Walter, Ulrich and Dietl, Johannes and Engel, Joerg B. and Honig, Arnd (2013) Immune escape of AKT overexpressing ovarian cancer cells. INTERNATIONAL JOURNAL OF ONCOLOGY, 42 (5). pp. 1630-1635. ISSN 1019-6439, 1791-2423

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Abstract

Platinum-resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. As survival is strongly influenced by immunological parameters, immunotherapeutic strategies appear promising. Therefore a better understanding of the interaction between ovarian tumour cells and cells of the immune system is a necessary prerequisite. In the present study we aimed to enlighten the interactions between platinum resistant and platinum sensitive ovarian cancer cells and natural-killer (NK)-cells. Modified FATAL assay was used for determining the killing efficiency of NK-cells for the parental A2780 cells and the cis-platinum resistant A2780cis human ovarian cancer cells. Expression of pro- and anti-apoptotic genes as well as ligands involved in NK-cell receptor recognition were analysed by RT-PCR and flow cytometric analysis. The efficiency of NK mediated cell lysis differs between A2780 cells and the cis-platinum-resistant A2780cis cells. A2780cis cells are less accessible for NK-cell mediated killing. Based on this observation we characterized the molecular basis for resistance mechanisms. Besides an increase in anti-apoptotic genes (especially CIAP-1 and -2) that probably render A2780cis cells more resistant against apoptosis an increased amount of soluble MICA/B seems to be responsible for the lower killing rate of platinum-resistant A2780cis cells compared to their parental A2780 cells.

Item Type: Article
Uncontrolled Keywords: PLATINUM RESISTANCE; PATHWAYS; IMMUNOSURVEILLANCE; INHIBITION; EXPRESSION; ROLES; LINES; GENE; ovarian cancer; AKT; platinum-resistance; natural-killer cells
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Apr 2020 14:04
Last Modified: 15 Apr 2020 14:04
URI: https://pred.uni-regensburg.de/id/eprint/16744

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