Fas ligand deficiency impairs tumor immunity by promoting an accumulation of monocytic myeloid-derived suppressor cells

Sanam Peyvandi, Stéphanie Buart, Boubekeur Samah, Marie Vétizou, Yanyan Zhang, Ludovic Durrieu, Mélanie Polrot, Salem Chouaib, Karim Benihoud, Fawzia Louache, Saoussen Karray

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26 Citations (Scopus)

Résumé

The Fas receptor ligand FasL regulates immune cell levels by inducing apoptosis of Fas receptor-positive cells. Here, we studied the impact of host FasL on tumor development in mice. Genetically targeting FasL in naïve mice increased myeloid cell populations, but, in marked contrast, it reduced the levels of myeloid-derived suppressor cells (MDSC) in mice bearing Lewis lung carcinoma tumors. Analysis of the MDSC subset distribution revealed that FasL deficiency skewed cell populations toward the M-MDSC subset, which displays a highly immunosuppressive activity. Furthermore, tumor-bearing mice that were FasL-deficient displayed an enhanced proportion of tumorassociated macrophages and regulatory T cells. Overall, the immunosuppressive environment produced by FasL targeting correlated with reduced survival of tumor-bearing mice. These results disclose a new role for FasL in modulating immunosuppressive cells.

langue originaleAnglais
Pages (de - à)4292-4301
Nombre de pages10
journalCancer Research
Volume75
Numéro de publication20
Les DOIs
étatPublié - 15 oct. 2015
Modification externeOui

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