4.6 Article

Immunoregulation and Clinical Implications of ANGPT2/TIE2+ M-MDSC Signature in Non-Small Cell Lung Cancer

Journal

CANCER IMMUNOLOGY RESEARCH
Volume 8, Issue 2, Pages 268-279

Publisher

AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-19-0326

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Funding

  1. Fonds de Dotation de Recherche en Sante Respiratoire
  2. La Ligue Contre le Cancer
  3. Conseil Regional de Franche-Comte
  4. Canceropole Grand Est

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Myeloid-derived suppressor cells (MDSC) promote immuno-suppression 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-MDSC) overexpressing TIE2, the receptor for angiopoietin-2 (ANGPT2), in patients with non-small cell lung cancer (NSCLC). Greater numbers of circulating TIE2(+) M-MDSCs were detected in patients with NSCLC compared with healthy subjects, and this accumulation correlated with ANGPT2 concentration in blood. The presence of an ANGPT2-rich environment was associated with impairment of preexisting T-cell responses against tumor-associated antigens (TAA) in patients with NSCLC. We demonstrated that ANGPT2 sensitizes TIE2(+) M-MDSCs such that these cells suppress TAA-specific T cells. In patients with NSCLC, 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.

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