TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells

Annamaria Biroccio, Julien Cherfils-Vicini, Adeline Augereau, Sébastien Pinte, Serge Bauwens, Jing Ye, Thomas Simonet, Béatrice Horard, Karine Jamet, Ludovic Cervera, Aaron Mendez-Bermudez, Delphine Poncet, Renée Grataroli, Claire T Kint De Rodenbeeke, Erica Salvati, Angela Rizzo, Pasquale Zizza, Michelle Ricoul, Céline Cognet, Thomas KuilmanHelene Duret, Florian Lépinasse, Jacqueline Marvel, Els Verhoeyen, François Loïc Cosset, Daniel Peeper, Mark J. Smyth, Arturo Londoño-Vallejo, Laure Sabatier, Vincent Picco, Gilles Pages, Jean Yves Scoazec, Antonella Stoppacciaro, Carlo Leonetti, Eric Vivier, Eric Gilson

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)818-828
Number of pages11
JournalNature Cell Biology
Volume15
Issue number7
DOIs
Publication statusPublished - Jul 2013

ASJC Scopus subject areas

  • Cell Biology

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    Biroccio, A., Cherfils-Vicini, J., Augereau, A., Pinte, S., Bauwens, S., Ye, J., Simonet, T., Horard, B., Jamet, K., Cervera, L., Mendez-Bermudez, A., Poncet, D., Grataroli, R., De Rodenbeeke, C. T. K., Salvati, E., Rizzo, A., Zizza, P., Ricoul, M., Cognet, C., ... Gilson, E. (2013). TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells. Nature Cell Biology, 15(7), 818-828. https://doi.org/10.1038/ncb2774