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树突状细胞在抗肿瘤 T 细胞反应和免疫原性肿瘤微环境的产生中起着关键作用,以抑制肿瘤的发展。

Crucial role of dendritic cells in the generation of anti-tumor T-cell responses and immunogenic tumor microenvironment to suppress tumor development.

机构信息

Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

出版信息

Front Immunol. 2024 Aug 14;15:1200461. doi: 10.3389/fimmu.2024.1200461. eCollection 2024.

DOI:10.3389/fimmu.2024.1200461
PMID:39206204
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11349553/
Abstract

Dendritic cells (DCs) are known as unique professional antigen (Ag)-presenting cells (APCs) to prime naïve T cells for the initiation of adaptive immunity. While DCs are believed to play a pivotal role in generating anti-tumor T-cell responses, the importance of DCs in the protection from the progression of tumors remains elusive. Here, we show how the constitutive deficiency of CD11c DCs influences the progression of tumors with the use of binary transgenic mice with constitutive loss of CD11c DCs. Constitutive loss of CD11c DCs not only enhances the progression of tumors but also reduces the responses of Ag-specific T cells. Furthermore, the congenital deficiency of CD11c DCs generates the immunosuppressive tumor microenvironment (TME) that correlates with the marked accumulation of myeloid-derived suppressor cells (MDSCs) and the prominent productions of immunosuppressive mediators. Thus, our findings suggest that CD11c DCs are crucial for generating anti-tumor T-cell responses and immunogenic TME to suppress the development of tumors.

摘要

树突状细胞 (DCs) 是已知的独特的专业抗原 (Ag)-呈递细胞 (APCs),可对初始 T 细胞进行初始免疫,从而产生适应性免疫。虽然人们认为 DCs 在产生抗肿瘤 T 细胞反应中发挥着关键作用,但 DCs 在保护肿瘤进展方面的重要性仍不清楚。在这里,我们展示了使用组成型缺失 CD11c DCs 的双转基因小鼠,研究组成型缺失 CD11c DCs 如何影响肿瘤的进展。组成型缺失 CD11c DCs 不仅会增强肿瘤的进展,还会降低 Ag 特异性 T 细胞的反应。此外,CD11c DCs 的先天性缺失会产生免疫抑制性肿瘤微环境 (TME),这与髓系来源的抑制性细胞 (MDSCs) 的显著积累和免疫抑制性介质的显著产生相关。因此,我们的研究结果表明,CD11c DCs 对于产生抗肿瘤 T 细胞反应和免疫原性 TME 以抑制肿瘤的发展至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/d0af33d97da0/fimmu-15-1200461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/a0a789780ded/fimmu-15-1200461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/9b203cc6324b/fimmu-15-1200461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/fcecbf63fd62/fimmu-15-1200461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/539098bacac4/fimmu-15-1200461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/d0af33d97da0/fimmu-15-1200461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/a0a789780ded/fimmu-15-1200461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/9b203cc6324b/fimmu-15-1200461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/fcecbf63fd62/fimmu-15-1200461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/539098bacac4/fimmu-15-1200461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4ea/11349553/d0af33d97da0/fimmu-15-1200461-g005.jpg

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