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

Cherfils-Vicini, Julien and Iltis, Charlene and Cervera, Ludovic and Pisano, Sabrina and Croce, Olivier and Győrffy, Balázs (2019) Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2. EMBO JOURNAL, 38 (11). ISSN 0261-4189

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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.

Item Type: Article
Uncontrolled Keywords: immunosurveillance; NK cells; HSPG; TRF2; MDSC;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Q Science / természettudomány > QR Microbiology / mikrobiológia > QR180 Immunology / immunológia
R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia
Depositing User: MTMT SWORD
Date Deposited: 27 Nov 2019 08:57
Last Modified: 27 Nov 2019 08:57

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