Immunoregulation and Clinical Implications of ANGPT2/TIE2+ M-MDSC Signature in Non-Small Cell Lung Cancer.
Fiche publication
Date publication
décembre 2019
Journal
Cancer immunology research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Pr BORG Christophe, Mme BOUARD Adeline, Mme LAHEURTE Caroline, Dr ASGAROV Kamal
Tous les auteurs :
Lauret Marie Joseph E, Laheurte C, Jary M, Boullerot L, Asgarov K, Gravelin E, Bouard A, Rangan L, Dosset M, Borg C, Adotévi O
Lien Pubmed
Résumé
Myeloid-derived suppressor cells (MDSCs) promote immunosuppression and are a target in the field of immuno-oncology. Accumulation of MDSCs is associated with poor prognosis and resistance to immunotherapy for several cancers. Here, we describe an accumulation of a subset of circulating monocytic MDSCs (M-MDSCs) overexpressing TIE2, the receptor for angiopoietin-2 (ANGPT2), in non-small cell lung cancer (NSCLC) patients. Greater numbers of circulating TIE2+ M-MDSCs were detected in NSCLC patients compared to healthy subjects and this accumulation correlated with ANGPT2 concentration in blood. The presence of an ANGPT2-rich environment was associated with impairment of pre-existing T-cell responses against tumor-associated antigens (TAAs) in NSCLC patients. We demonstrated that ANGPT2 sensitizes TIE2+ M-MDSCs such that these cells suppress TAA-specific T cells. In NSCLC patients, upregulation of the ANGPT2/TIE2+ M-MDSC signature in blood was associated with a poor prognosis. Our results identify the ANGPT2/TIE2+ M-MDSC axis as a participant in tumor immune evasion that should be taken into account in future cancer immunotherapy.
Référence
Cancer Immunol Res. 2019 Dec 23;: