Stromal Immunology Laboratory, MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom.
Front Immunol. 2022 Mar 10;13:733800. doi: 10.3389/fimmu.2022.733800. eCollection 2022.
The tumour microenvironment (TME) presents a major block to anti-tumour immune responses and to effective cancer immunotherapy. The inflammatory mediators such as cytokines, chemokines, growth factors and prostaglandins generated in the TME alter the phenotype and function of dendritic cells (DCs) that are critical for a successful adaptive immune response against the growing tumour. In this mini review we discuss how tumour cells and the surrounding stroma modulate DC maturation and trafficking to impact T cell function. Fibroblastic stroma and the associated extracellular matrix around tumours can also provide physical restrictions to infiltrating DCs and other leukocytes. We discuss interactions between the inflammatory TME and infiltrating immune cell function, exploring how the inflammatory TME affects generation of T cell-driven anti-tumour immunity. We discuss the open question of the relative importance of antigen-presentation site; locally within the TME versus tumour-draining lymph nodes. Addressing these questions will potentially increase immune surveillance and enhance anti-tumour immunity.
肿瘤微环境 (TME) 对抗肿瘤免疫反应和有效的癌症免疫治疗构成了重大障碍。TME 中产生的炎症介质,如细胞因子、趋化因子、生长因子和前列腺素,改变了树突状细胞 (DC) 的表型和功能,而 DC 对针对不断生长的肿瘤的适应性免疫反应至关重要。在这篇迷你综述中,我们讨论了肿瘤细胞和周围基质如何调节 DC 的成熟和迁移,从而影响 T 细胞的功能。肿瘤周围的纤维性基质和相关细胞外基质也可以为浸润的 DC 和其他白细胞提供物理限制。我们讨论了炎症性 TME 与浸润免疫细胞功能之间的相互作用,探讨了炎症性 TME 如何影响 T 细胞驱动的抗肿瘤免疫的产生。我们讨论了抗原呈递部位的相对重要性的开放性问题,即局部位于 TME 内还是肿瘤引流淋巴结内。解决这些问题将有可能增强免疫监视并增强抗肿瘤免疫。