Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer.

Détails

ID Serval
serval:BIB_23F6031897C7
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer.
Périodique
Nature
Auteur(s)
Di Mitri D., Toso A., Chen J.J., Sarti M., Pinton S., Jost T.R., D'Antuono R., Montani E., Garcia-Escudero R., Guccini I., Da Silva-Alvarez S., Collado M., Eisenberger M., Zhang Z., Catapano C., Grassi F., Alimonti A.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
515
Numéro
7525
Pages
134-137
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.Publication Status: ppublish
Résumé
Aberrant activation of oncogenes or loss of tumour suppressor genes opposes malignant transformation by triggering a stable arrest in cell growth, which is termed cellular senescence. This process is finely tuned by both cell-autonomous and non-cell-autonomous mechanisms that regulate the entry of tumour cells to senescence. Whether tumour-infiltrating immune cells can oppose senescence is unknown. Here we show that at the onset of senescence, PTEN null prostate tumours in mice are massively infiltrated by a population of CD11b(+)Gr-1(+) myeloid cells that protect a fraction of proliferating tumour cells from senescence, thus sustaining tumour growth. Mechanistically, we found that Gr-1(+) cells antagonize senescence in a paracrine manner by interfering with the senescence-associated secretory phenotype of the tumour through the secretion of interleukin-1 receptor antagonist (IL-1RA). Strikingly, Pten-loss-induced cellular senescence was enhanced in vivo when Il1ra knockout myeloid cells were adoptively transferred to PTEN null mice. Therapeutically, docetaxel-induced senescence and efficacy were higher in PTEN null tumours when the percentage of tumour-infiltrating CD11b(+)Gr-1(+) myeloid cells was reduced using an antagonist of CXC chemokine receptor 2 (CXCR2). Taken together, our findings identify a novel non-cell-autonomous network, established by innate immunity, that controls senescence evasion and chemoresistance. Targeting this network provides novel opportunities for cancer therapy.
Mots-clé
Animals, Cell Aging/drug effects, Cell Movement, Disease Progression, Drug Resistance, Neoplasm, Humans, Immunity, Innate, Interleukin 1 Receptor Antagonist Protein/deficiency, Interleukin 1 Receptor Antagonist Protein/metabolism, Interleukin-1alpha/immunology, Interleukin-1alpha/metabolism, Male, Mice, Myeloid Cells/cytology, Myeloid Cells/metabolism, PTEN Phosphohydrolase/deficiency, PTEN Phosphohydrolase/genetics, Prostatic Neoplasms/drug therapy, Prostatic Neoplasms/immunology, Receptors, Chemokine/metabolism, Receptors, Interleukin-8B/antagonists & inhibitors, Taxoids/pharmacology, Tumor Escape, Tumor Microenvironment
Pubmed
Web of science
Création de la notice
18/10/2016 16:35
Dernière modification de la notice
03/03/2018 14:56
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