Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium.
Myeloid Cell Immunology Lab, VIB Center for Inflammation Research, Brussels, Belgium; Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; INSERM, 101 rue Tolbiac, Paris 75013, France.
Cell Immunol. 2021 Apr;362:104296. doi: 10.1016/j.cellimm.2021.104296. Epub 2021 Jan 30.
Efficient priming of anti-tumor T cells requires the uptake and presentation of tumor antigens by immunogenic dendritic cells (DCs) and occurs mainly in lymph nodes draining the tumor (tdLNs). However, tumors expand and activate myeloid-derived suppressor cells (MDSCs) that inhibit CTL functions by several mechanisms. While the immune-suppressive nature of the tumor microenvironment is largely documented, it is not known whether similar immune-suppressive mechanisms operate in the tdLNs. In this study, we analyzed MDSC characteristics within tdLNs. We show that, in a metastasis-free context, MO-MDSCs are the dominant MDSC population within tdLNs, that they are highly suppressive and that tumor proximity enhances their recruitment to tdLN via a CCR2/CCL2-dependent pathway. Altogether our results uncover a mechanism by which tumors evade the immune system that involves MDSC-mediated recruitment to the tdLN and the inhibition of T-cell activation even before reaching the highly immunosuppressive tumor microenvironment.
有效的抗肿瘤 T 细胞启动需要免疫原性树突状细胞（DC）摄取和呈递肿瘤抗原，主要发生在肿瘤引流的淋巴结（tdLNs）中。然而，肿瘤会扩张并激活髓源抑制性细胞（MDSCs），通过多种机制抑制 CTL 功能。虽然肿瘤微环境的免疫抑制性质已被广泛记录，但尚不清楚类似的免疫抑制机制是否在 tdLNs 中起作用。在这项研究中，我们分析了 tdLNs 中的 MDSC 特征。我们表明，在无转移的情况下，MO-MDSCs 是 tdLNs 中主要的 MDSC 群体，它们具有高度的抑制作用，并且肿瘤的临近通过 CCR2/CCL2 依赖性途径增强了它们向 tdLN 的募集。总之，我们的研究结果揭示了一种肿瘤逃避免疫系统的机制，涉及 MDSC 介导的向 tdLN 的募集以及 T 细胞激活的抑制，甚至在到达高度免疫抑制的肿瘤微环境之前就已经发生。
