Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2 - Université Claude Bernard Lyon 1 Accéder directement au contenu
Article Dans Une Revue EMBO Journal Année : 2019

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

Romy Collet
  • Fonction : Auteur
Valerie M. Renault
  • Fonction : Auteur
Martin Rey-Millet
  • Fonction : Auteur
Carlo Leonetti
  • Fonction : Auteur
Fabrice Allain
Nicolas Soubeiran
  • Fonction : Auteur
Marina Shkreli
Charlene Iltis
  • Fonction : Auteur
Ludovic Cervera
  • Fonction : Auteur
Olivier Croce
Nori Sadouni
  • Fonction : Auteur

Résumé

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.

Domaines

Immunologie

Dates et versions

hal-02359442 , version 1 (12-11-2019)

Identifiants

Citer

Balazs Gyorffy, Romy Collet, Valerie M. Renault, Martin Rey-Millet, Carlo Leonetti, et al.. Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2. EMBO Journal, 2019, 38 (11), ⟨10.15252/embj.2018100012⟩. ⟨hal-02359442⟩
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