Immunoregulation and Clinical Implications of ANGPT2/TIE2+ M-MDSC Signature in Non-Small Cell Lung Cancer
Immunoregulation and Clinical Implications of ANGPT2/TIE2+ M-MDSC Signature in Non-Small Cell Lung Cancer
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ANGPT2/TIE2+ M-MDSC 特征在非小细胞肺癌中的免疫调节和临床意义
DOI：
10.1158/2326-6066.cir-19-0326
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发表时间：
2020-02-01
影响因子：
10.1
通讯作者：
Adotevi, Olivier
中科院分区：
文献类型：
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作者：
Joseph, Elodie Lauret Marie;Laheurte, Caroline;Adotevi, Olivier
骨髓源性抑制细胞（MDSC）促进免疫抑制，并且是免疫肿瘤学领域中的靶标。MDSC的积累与几种癌症的不良预后和对免疫疗法的抗性相关。在此，我们描述了非小细胞肺癌（NSCLC）患者中循环单核细胞MDSC（M-MDSC）亚群过度表达血管生成素2（ANGPT 2）受体TIE 2的蓄积。与健康受试者相比，在NSCLC患者中检测到更多数量的循环TIE 2（+）M-MDSC，并且这种蓄积与血液中ANGPT 2浓度相关。ANGPT 2富集环境的存在与NSCLC患者中针对肿瘤相关抗原（TAA）的既存T细胞应答受损相关。我们证明ANGPT 2使TIE 2（+）M-MDSC敏感，使得这些细胞抑制TAA特异性T细胞。在NSCLC患者中，血液中ANGPT 2/TIE 2（+）M-MDSC标记的上调与不良预后相关。我们的研究结果确定ANGPT 2/TIE 2（+）M-MDSC轴作为肿瘤免疫逃避的参与者，在未来的癌症免疫治疗中应考虑到这一点。
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.