دورية أكاديمية
Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity
| العنوان: | Tumour-retained activated CCR7+ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity |
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| المؤلفون: | Lee, Colin Y. C., Kennedy, Bethany C., Richoz, Nathan, Dean, Isaac, Tuong, Zewen K., Gaspal, Fabrina, Li, Zhi, Willis, Claire, Hasegawa, Tetsuo, Whiteside, Sarah K., Posner, David A., Carlesso, Gianluca, Hammond, Scott A., Dovedi, Simon J., Roychoudhuri, Rahul, Withers, David R., Clatworthy, Menna R. |
| المساهمون: | Wellcome Trust, Cancer Research UK |
| المصدر: | Nature Communications ; volume 15, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-024-44787-1 |
| الإتاحة: | https://doi.org/10.1038/s41467-024-44787-1Test https://www.nature.com/articles/s41467-024-44787-1.pdfTest https://www.nature.com/articles/s41467-024-44787-1Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.80EFBBF1 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-024-44787-1 |
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