Section Molecular Immunology, Institute of Immunology, Heidelberg University Hospital, 69120 Heidelberg, Germany.
Int J Mol Sci. 2021 May 27;22(11):5736. doi: 10.3390/ijms22115736.
The understanding of the tumor microenvironment (TME) has been expanding in recent years in the context of interactions among different cell types, through direct cell-cell communication as well as through soluble factors. It has become evident that the development of a successful antitumor response depends on several TME factors. In this context, the number, type, and subsets of immune cells, as well as the functionality, memory, and exhaustion state of leukocytes are key factors of the TME. Both the presence and functionality of immune cells, in particular T cells, are regulated by cellular and soluble factors of the TME. In this regard, one fundamental reason for failure of antitumor responses is hijacked immune cells, which contribute to the immunosuppressive TME in multiple ways. Specifically, reactive oxygen species (ROS), metabolites, and anti-inflammatory cytokines have central roles in generating an immunosuppressive TME. In this review, we focused on recent developments in the immune cell constituents of the TME, and the micromilieu control of antitumor responses. Furthermore, we highlighted the current challenges of T cell-based immunotherapies and potential future strategies to consider for strengthening their effectiveness.
近年来，人们在不同细胞类型之间的相互作用的背景下，通过直接的细胞间通讯以及可溶性因子，对肿瘤微环境（TME）的理解不断扩展。显然，成功的抗肿瘤反应的发展取决于几个 TME 因素。在这种情况下，免疫细胞的数量、类型和亚群，以及白细胞的功能、记忆和耗竭状态是 TME 的关键因素。免疫细胞，特别是 T 细胞的存在和功能都受到 TME 的细胞和可溶性因子的调节。在这方面，抗肿瘤反应失败的一个根本原因是被劫持的免疫细胞，它们通过多种方式促成了免疫抑制的 TME。具体而言，活性氧（ROS）、代谢物和抗炎细胞因子在产生免疫抑制性 TME 方面起着核心作用。在这篇综述中，我们重点介绍了 TME 中免疫细胞成分的最新进展，以及抗肿瘤反应的微环境控制。此外，我们强调了基于 T 细胞的免疫疗法目前面临的挑战，并提出了一些潜在的未来策略来考虑，以增强其疗效。
