Haist Maximilian, Stege Henner, Grabbe Stephan, Bros Matthias
Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.
Cancers (Basel). 2021 Jan 8;13(2):210. doi: 10.3390/cancers13020210.
Immune checkpoint inhibitors (ICI) have led to profound and durable tumor regression in some patients with metastatic cancer diseases. However, many patients still do not derive benefit from immunotherapy. Here, the accumulation of immunosuppressive cell populations within the tumor microenvironment (TME), such as myeloid-derived suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory T cells (Treg), contributes to the development of immune resistance. MDSC and Treg expand systematically in tumor patients and inhibit T cell activation and T effector cell function. Numerous studies have shown that the immunosuppressive mechanisms exerted by those inhibitory cell populations comprise soluble immunomodulatory mediators and receptor interactions. The latter are also required for the crosstalk of MDSC and Treg, raising questions about the relevance of cell-cell contacts for the establishment of their inhibitory properties. This review aims to outline the current knowledge on the crosstalk between these two cell populations, issuing particularly the potential role of cell adhesion molecules. In this regard, we further discuss the relevance of β2 integrins, which are essential for the differentiation and function of leukocytes as well as for MDSC-Treg interaction. Lastly, we aim to describe the impact of such bidirectional crosstalk for basic and applied cancer research and discuss how the targeting of these pathways might pave the way for future approaches in immunotherapy.
免疫检查点抑制剂（ICI）已使一些转移性癌症患者实现了深度且持久的肿瘤消退。然而，许多患者仍无法从免疫疗法中获益。肿瘤微环境（TME）中免疫抑制细胞群体的积累，如髓源性抑制细胞（MDSC）、肿瘤相关巨噬细胞（TAM）和调节性T细胞（Treg），导致了免疫抗性的产生。MDSC和Treg在肿瘤患者体内系统性扩增，并抑制T细胞活化和T效应细胞功能。众多研究表明，这些抑制性细胞群体发挥的免疫抑制机制包括可溶性免疫调节介质和受体相互作用。后者也是MDSC和Treg相互作用所必需的，这引发了关于细胞间接触对于其抑制特性建立的相关性的疑问。本综述旨在概述目前关于这两种细胞群体间相互作用的知识，特别关注细胞黏附分子的潜在作用。在这方面，我们进一步讨论β2整合素的相关性，其对于白细胞的分化和功能以及MDSC-Treg相互作用至关重要。最后，我们旨在描述这种双向相互作用对基础和应用癌症研究的影响，并讨论靶向这些途径如何可能为未来的免疫治疗方法铺平道路。
