Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Ashton Street, Liverpool L69 3GE, UK.
Cells. 2019 Jul 19;8(7):747. doi: 10.3390/cells8070747.
Despite the incredible clinical benefits obtained by the use of immune checkpoint blockers (ICBs), resistance is still common for many types of cancer. Central for ICBs to work is activation and infiltration of cytotoxic CD8 T cells following tumour-antigen recognition. However, it is now accepted that even in the case of immunogenic tumours, the effector functions of CD8 T cells are highly compromised by the presence of an immunosuppressive tumour microenvironment (TME) at the tumour site. Tumour-associated macrophages (TAMs) are among the most abundant non-malignant stromal cell types within the TME and they are crucial drivers of tumour progression, metastasis and resistance to therapy. TAMs are able to regulate either directly or indirectly various aspects of tumour immunity, including T cell recruitment and functions. In this review we discuss the mechanisms by which TAMs subvert CD8 T cell immune surveillance and how their targeting in combination with ICBs represents a very powerful therapeutic strategy.
尽管免疫检查点抑制剂 (ICBs) 的使用带来了令人难以置信的临床获益，但许多类型的癌症仍然存在耐药性。ICBs 发挥作用的关键是在肿瘤抗原识别后，细胞毒性 CD8 T 细胞的激活和浸润。然而，现在人们已经接受，即使是在免疫原性肿瘤的情况下，CD8 T 细胞的效应功能也受到肿瘤部位免疫抑制肿瘤微环境 (TME) 的严重损害。肿瘤相关巨噬细胞 (TAMs) 是 TME 中最丰富的非恶性基质细胞类型之一，它们是肿瘤进展、转移和对治疗耐药的关键驱动因素。TAMs 能够直接或间接地调节肿瘤免疫的各个方面，包括 T 细胞的募集和功能。在这篇综述中，我们讨论了 TAMs 颠覆 CD8 T 细胞免疫监视的机制，以及它们与 ICBs 联合靶向治疗的策略。
