Abstracts (complete list) - Wissenschaft Online

Sonja Textor, Rosita Accardi, Matthias Dürst, Massimo Tommasino, Lutz Gissmann,
Adelheid Cerwenka
Up-regulated expression of activating NK cell receptor ligands
in human cervical cancer
NK cell activation is mediated by a delicate balance of signals received by activating and
inhibiting receptors. Certain activating receptors recognize ligands, which are induced
upon cellular stress like transformation or viral infection. Inhibitory signals are delivered
to NK cells through interaction with self MHC class I or related molecules. Expression of
these ligands is modulated by certain viruses and on tumors rendering the infected or
transformed cells more or less susceptible to NK cell attack.
The aim of our study was to evaluate the impact of the two major transforming
oncogenes of Human Papilloma Viruses (HPV), E6 and E7, on the regulation of NK cell
receptor ligand expression. First, we analysed the expression of NK cell receptor ligands
on keratinocytes after transduction with a retroviral vector system carrying HPV16-E6
and/or -E7 by flow cytometry. Comparing HPV16-E6E7 expressing keratinocytes with
the corresponding parental cells, we detected up-regulation of MICA, a ligand for the
activating NK cell receptor NKG2D. Expression of other ligands, like CD155, a ligand for
the activating NK cell receptor DNAM-1, remained unchanged.
Since high-risk HPVs, like HPV16, are the etiological agents of cervical cancer (CxCa),
biopsies of CxCa and prelesions were stained for NK cell receptor ligands and NK cells
by immuno-histochemistry in situ. Tumor-infiltrating NK cells (CD56+) were found in all
cervical cancer stages. High expression of the activating NK cell receptor ligands, MICA
and CD155, was only observed in CxCa specimens, whereas precursor lesions showed
no MICA expression und moderate CD155 expression. Some CxCa biopsies showed low
MHC class I expression in combination with high expression of activating NK cell
receptor ligands, making CxCa an appealing target for NK cell- based immunotherapy.