Andrea, Rome, Italy, 3 Regina Elena Cancer Institute, Rome, Italy, 4 Centre d’Immunologie de Marseille-Luminy, Université

Selleckchem VX-661 de la Méditerranée, Marseille, France check details Several recent data showed that deprotected telomeres can suppress oncogenesis by engaging senescence or apoptosis, providing an explanation for the up-regulation of telomerase observed in the vast majority of human cancers. Interestingly, an increased dosage of TRF2, a key factor to preserve telomere protection and acting independently of the telomerase pathway, is also observed in various human malignancies and contributes to carcinogenesis in mice. However, very little is known on the role of TRF2 in cancer. We demonstrate here that a reduced activity or expression of TRF2 in human tumor cells can impair their ability to form xenografts in immunocompromised mice without engaging a cell intrinsic program of proliferation arrest. Strikingly, this antitumor effect does not correlate with overt telomere deprotection, DNA damage response and senescence. These data suggest that cell extrinsic mechanisms limit tumor formation upon TRF2 inhibition.

We further demonstrate that the anti-tumor properties of TRF2 inhibition rely on activation of natural killer (NK) cells. These findings suggest that the overexpression of TRF2 observed in different types of human cancer contributes to bypass innate immunosurveillance. Consequently, TRF2 emerges as a multifunctional oncogenic protein and a promising therapeutic target. Poster Unoprostone No. 162 Therapy of Minimal Residual Tumour Disease: β-galactosylceramide Inhibits Growth of Recurrent HPV16-associated Neoplasms after Surgery and Chemotherapy AZD6738 mouse Jana Šímová 1 , Marie Indrová1, Jana Bieblová1, Romana Mikyšková1, Jan Bubeník1,

Milan Reiniš1 1 Department of Tumour Immunology, Institute of Molecular Genetics AS CR, Prague, Czech Republic Natural killer T (NKT) cells are potent modulators of anti-tumour immunity. Their protective effects can be achieved upon their activation by glycolipid ligands presented in the context of the CD1d molecule. These CD1d-binding glycolipid antigens have been described as potent therapeutic agents against tumours, infections, as well as autoimmune diseases. On the other hand, their repeated administration can result in NKT cell anergy and serious adverse effects. Immunoregulatory and therapeutic effects of glycolipid ligands depend on their structure and modes of administration. Therefore more studies are needed for optimization of the particular therapeutic settings. This study was focused on tumour-inhibitory effects of 12 carbon acyl chain β-galactosylceramide (C12 β-D-GalactosylCeramide) on the growth of HPV16-associated neoplasms transplanted in the syngeneic mice. Treatment of tumour bearing mice with β-galactosylceramide 3–14 days after transplantation of tumour cells significantly inhibited growth of the MHC class I-positive (TC-1), as well as MHC class I-deficient (TC-1/A9) HPV16-asssociated tumours.