Research Division of the Department of Otorhinolaryngology, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany.
Institute of Virology, University Hospital Essen, University Duisburg-Essen, D-45122 Essen, Germany.
Nat Commun. 2017 Mar 16;8:14600. doi: 10.1038/ncomms14600.
Toll-like receptors (TLRs) are located either on the cell surface or intracellularly in endosomes and their activation normally contributes to the induction of protective immune responses. However, in cancer their activation by endogenous ligands can modulate tumour progression. It is currently unknown how endosomal TLRs regulate endogenous anti-tumour immunity. Here we show that TLR3, 7 and 9 deficiencies on host cells, after initial tumour growth, result in complete tumour regression and induction of anti-tumour immunity. Tumour regression requires the combined absence of all three receptors, is dependent on both CD4 and CD8 T cells and protects the mice from subsequent tumour challenge. While tumours in control mice are infiltrated by higher numbers of regulatory T cells, tumour regression in TLR-deficient mice is paralleled by altered vascular structure and strongly induced influx of cytotoxic and cytokine-producing effector T cells. Thus, endosomal TLRs may represent a molecular link between the inflamed tumour cell phenotype, anti-tumour immunity and the regulation of T-cell activation.
Toll 样受体 (TLRs) 位于细胞表面或细胞内的内体中，其激活通常有助于诱导保护性免疫反应。然而，在癌症中，内体 TLR 的激活可以调节肿瘤的进展。目前尚不清楚内体 TLR 如何调节内源性抗肿瘤免疫。在这里，我们表明，宿主细胞中 TLR3、7 和 9 的缺失，在初始肿瘤生长后，会导致完全的肿瘤消退和抗肿瘤免疫的诱导。肿瘤消退需要所有三种受体的联合缺失，依赖于 CD4 和 CD8 T 细胞，并保护小鼠免受随后的肿瘤挑战。虽然对照小鼠的肿瘤中浸润了更多数量的调节性 T 细胞，但 TLR 缺陷型小鼠的肿瘤消退伴随着血管结构的改变和细胞毒性和细胞因子产生的效应 T 细胞的强烈流入。因此，内体 TLR 可能是炎症肿瘤细胞表型、抗肿瘤免疫和 T 细胞激活调节之间的分子联系。
