Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2

Julien Cherfils-Vicini, Charlene Iltis, Ludovic Cervera, Sabrina Pisano, Olivier Croce, Nori Sadouni, Balázs Győrffy, Romy Collet, Valérie M. Renault, Martin Rey-Millet, Carlo Leonetti, Pasquale Zizza, Fabrice Allain, Francois Ghiringhelli, Nicolas Soubeiran, Marina Shkreli, Eric Vivier, Annamaria Biroccio, Eric Gilson

Research output: Contribution to journalArticle

Abstract

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSCs in human cancers by upregulating TRF2, a protein required for telomere stability. Specifically, we showed that the TRF2 upregulation in cancer cells has extratelomeric roles in activating the expression of a network of genes involved in the biosynthesis of heparan sulfate proteoglycan, leading to profound changes in glycocalyx length and stiffness, as revealed by atomic force microscopy. This TRF2-dependent regulation facilitated the recruitment of MDSCs, their activation via the TLR2/MyD88/IL-6/STAT3 pathway leading to the inhibition of natural killer recruitment and cytotoxicity, and ultimately tumor progression and metastasis. The clinical relevance of these findings is supported by our analysis of cancer cohorts, which showed a correlation between high TRF2 expression and MDSC infiltration, which was inversely correlated with overall patient survival.

Original languageEnglish
JournalEMBO Journal
Volume38
Issue number11
DOIs
Publication statusPublished - Jun 3 2019

Keywords

  • HSPG
  • immunosurveillance
  • MDSC
  • NK cells
  • TRF2

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Cherfils-Vicini, J., Iltis, C., Cervera, L., Pisano, S., Croce, O., Sadouni, N., Győrffy, B., Collet, R., Renault, V. M., Rey-Millet, M., Leonetti, C., Zizza, P., Allain, F., Ghiringhelli, F., Soubeiran, N., Shkreli, M., Vivier, E., Biroccio, A., & Gilson, E. (2019). Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2. EMBO Journal, 38(11). https://doi.org/10.15252/embj.2018100012