Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7⁺ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7⁺ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7⁺ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7⁺ DCs co-localise with PD-1⁺CD8⁺ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7⁺ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.

肿瘤树突状细胞 （DC） 内化抗原并上调 CCR7，从而引导它们迁移到肿瘤引流淋巴结 （dLN）。CCR7 表达与富含调节分子表达（包括 PD-L1）的激活程序偶联。然而，CCR7 ⁺ DC 在抗肿瘤免疫反应中的时空动力学仍不清楚。在这里，我们使用光转换鼠标来精确跟踪 DC 迁移。我们报道 CCR7 ⁺ DC 是迁移到 dLN 的主要 DC 群体，但尽管 CCR7 表达，但仍有一部分仍然驻留在肿瘤中。这些肿瘤保留的 CCR7 ⁺ DC 在表型和转录上与其 dLN 对应物不同且具有异质性。此外，它们随着肿瘤停留时间的延长而逐渐下调抗原呈递和促炎转录物的表达。在人和小鼠实体瘤中，驻留在肿瘤中的 CCR7 ⁺ DC 与 PD-1 ⁺ CD8 ⁺ T 细胞共定位，并且在抗 PD-L1 治疗后，上调包括 OX40L 在内的刺激分子，从而增强抗肿瘤溶细胞活性。总而言之，这些数据揭示了 CCR7⁺ DC 中以前未被重视的异质性，这可能支持支持肿瘤内细胞毒性 T 细胞的可变能力。