Myeloid-derived suppressor cells (MDSC) 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-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.

中文翻译：

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非小细胞肺癌中ANGPT2 / TIE2 + M-MDSC签名的免疫调节及其临床意义。

骨髓来源的抑制细胞（MDSC）促进免疫抑制，是免疫肿瘤学领域的目标。MDSC的积累与几种癌症的不良预后和对免疫疗法的抵抗力有关。在这里，我们描述了非小细胞肺癌（NSCLC）患者中过度表达TIE2（血管生成素2受体）的循环单核MDSC（M-MDSC）子集的积累。与健康受试者相比，NSCLC患者中检测到更多的循环TIE2 + M-MDSC，并且这种积累与血液中ANGPT2浓度相关。NSCLC患者中富含ANGPT2的环境的存在与先前针对肿瘤相关抗原（TAA）的T细胞反应的损伤相关。我们证明了ANGPT2使TIE2 + M-MDSCs敏感，从而使这些细胞抑制TAA特异性T细胞。在NSCLC患者中，血液中ANGPT2 / TIE2 + M-MDSC信号的上调与不良预后相关。我们的研究结果确定ANGPT2 / TIE2 + M-MDSC轴是肿瘤免疫逃逸的参与者，在未来的癌症免疫治疗中应考虑到这一点。