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 Kuilman; Helene 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

doi:10.1038/ncb2774

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

Istituto Regina Elena

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	818-828
Number of pages	11
Journal	Nature Cell Biology
Volume	15
Issue number	7
DOIs	https://doi.org/10.1038/ncb2774
Publication status	Published - 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

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, CTK, Salvati, E, Rizzo, A, Zizza, P, Ricoul, M, Cognet, C, Kuilman, T, Duret, H, Lépinasse, F, Marvel, J, Verhoeyen, E, Cosset, FL, Peeper, D, Smyth, MJ, Londoño-Vallejo, A, Sabatier, L, Picco, V, Pages, G, Scoazec, JY, Stoppacciaro, A, Leonetti, C, Vivier, E & Gilson, E 2013, 'TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells', Nature Cell Biology, vol. 15, no. 7, pp. 818-828. https://doi.org/10.1038/ncb2774

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title = "TRF2 inhibits a cell-extrinsic pathway through which natural killer cells eliminate cancer cells",

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.",

author = "Annamaria Biroccio and Julien Cherfils-Vicini and Adeline Augereau and S{\'e}bastien Pinte and Serge Bauwens and Jing Ye and Thomas Simonet and B{\'e}atrice Horard and Karine Jamet and Ludovic Cervera and Aaron Mendez-Bermudez and Delphine Poncet and Ren{\'e}e Grataroli and {De Rodenbeeke}, {Claire T Kint} and Erica Salvati and Angela Rizzo and Pasquale Zizza and Michelle Ricoul and C{\'e}line Cognet and Thomas Kuilman and Helene Duret and Florian L{\'e}pinasse and Jacqueline Marvel and Els Verhoeyen and Cosset, {Fran{\c c}ois Lo{\"i}c} and Daniel Peeper and Smyth, {Mark J.} and Arturo Londo{\~n}o-Vallejo and Laure Sabatier and Vincent Picco and Gilles Pages and Scoazec, {Jean Yves} and Antonella Stoppacciaro and Carlo Leonetti and Eric Vivier and Eric Gilson",

year = "2013",

month = jul,

doi = "10.1038/ncb2774",

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AU - Biroccio, Annamaria

AU - Cherfils-Vicini, Julien

AU - Augereau, Adeline

AU - Pinte, Sébastien

AU - Bauwens, Serge

AU - Ye, Jing

AU - Simonet, Thomas

AU - Horard, Béatrice

AU - Jamet, Karine

AU - Cervera, Ludovic

AU - Mendez-Bermudez, Aaron

AU - Poncet, Delphine

AU - Grataroli, Renée

AU - De Rodenbeeke, Claire T Kint

AU - Salvati, Erica

AU - Rizzo, Angela

AU - Zizza, Pasquale

AU - Ricoul, Michelle

AU - Cognet, Céline

AU - Kuilman, Thomas

AU - Duret, Helene

AU - Lépinasse, Florian

AU - Marvel, Jacqueline

AU - Verhoeyen, Els

AU - Cosset, François Loïc

AU - Peeper, Daniel

AU - Smyth, Mark J.

AU - Londoño-Vallejo, Arturo

AU - Sabatier, Laure

AU - Picco, Vincent

AU - Pages, Gilles

AU - Scoazec, Jean Yves

AU - Stoppacciaro, Antonella

AU - Leonetti, Carlo

AU - Vivier, Eric

AU - Gilson, Eric

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

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

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