TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells
- Creators
- Biroccio, Annamaria
- Cherfils-Vicini, Julien
- Augereau, Adeline
- Pinte, Sébastien
- Bauwens, Serge
- Ye, Jing
- Simonet, Thomas
- Horard, Béatrice
- Jamet, Karine
- Cervera, Ludovic
- Mendez-Bermudez, Aaron
- Poncet, Delphine
- Grataroli, Renée
- de Rodenbeeke, Claire t'Kint
- Salvati, Erica
- Rizzo, Angela
- Zizza, Pasquale
- Ricoul, Michelle
- Cognet, Céline
- Kuilman, Thomas
- Duret, Helene
- Lépinasse, Florian
- Marvel, Jacqueline
- Verhoeyen, Els
- Cosset, François-Loïc
- Peeper, Daniel
- Smyth, Mark
- Londoño-Vallejo, Arturo
- Sabatier, Laure
- Picco, Vincent
- Pages, Gilles
- Scoazec, Jean-Yves
- Stoppacciaro, Antonella
- Leonetti, Carlo
- Vivier, Eric
- Gilson, Eric
- de Rodenbeeke, Claire T'kint
- Others:
- Experimental Chemotherapy Laboratory ; Regina Elena Cancer Institute
- Institut de Recherche sur le Cancer et le Vieillissement (IRCAN) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Laboratoire de Biologie Moléculaire de la Cellule (LBMC) ; École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239) ; École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Description
Dysfunctional telomeres suppress tumour progression by activating cell-intrinsic programs that lead to growth arrest. Increased levels of TRF2, a key factor in telomere protection, are observed in various human malignancies and contribute to oncogenesis. We demonstrate here that a high level of TRF2 in tumour cells decreased their ability to recruit and activate natural killer (NK) cells. Conversely, a reduced dose of TRF2 enabled tumour cells to be more easily eliminated by NK cells. Consistent with these results, a progressive upregulation of TRF2 correlated with decreased NK cell density during the early development of human colon cancer. By screening for TRF2-bound genes, we found that HS3ST4--a gene encoding for the heparan sulphate (glucosamine) 3-O-sulphotransferase 4--was regulated by TRF2 and inhibited the recruitment of NK cells in an epistatic relationship with TRF2. Overall, these results reveal a TRF2-dependent pathway that is tumour-cell extrinsic and regulates NK cell immunity.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-03510917
- URN
- urn:oai:HAL:hal-03510917v1
- Origin repository
- UNICA