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Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF 2
Author(s) -
CherfilsVicini Julien,
Iltis Charlene,
Cervera Ludovic,
Pisano Sabrina,
Croce Olivier,
Sadouni Nori,
Győrffy Balázs,
Collet Romy,
Renault Valérie M,
ReyMillet Martin,
Leonetti Carlo,
Zizza Pasquale,
Allain Fabrice,
Ghiringhelli Francois,
Soubeiran Nicolas,
Shkreli Marina,
Vivier Eric,
Biroccio Annamaria,
Gilson Eric
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018100012
Subject(s) - biology , downregulation and upregulation , cancer cell , cancer research , immune system , glycocalyx , tumor progression , metastasis , cancer , microbiology and biotechnology , immunology , gene , genetics
Myeloid‐derived suppressor cells ( MDSC s) are immature myeloid cells with strong immunosuppressive activity that promote tumor growth. In this study, we describe a mechanism by which cancer cells control MDSC s in human cancers by upregulating TRF 2, a protein required for telomere stability. Specifically, we showed that the TRF 2 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 TRF 2‐dependent regulation facilitated the recruitment of MDSC s, their activation via the TLR 2/MyD88/ IL ‐6/ STAT 3 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 TRF 2 expression and MDSC infiltration, which was inversely correlated with overall patient survival.