GSTDTAP  > 地球科学
DOI10.1038/s41586-020-2134-y
A conserved dendritic-cell regulatory program limits antitumour immunity
Perry, Rachel J.1,2; Zhang, Dongyan1; Guerra, Mateus T.1; Brill, Allison L.2; Goedeke, Leigh1; Nasiri, Ali R.1; Rabin-Court, Aviva1; Wang, Yongliang1; Peng, Liang1; Dufour, Sylvie1; Zhang, Ye1; Zhang, Xian-Man1; Butrico, Gina M.1; Toussaint, Keshia1; Nozaki, Yuichi1; Cline, Gary W.1; Petersen, Kitt Falk1; Nathanson, Michael H.1; Ehrlich, Barbara E.2,3; Shulman, Gerald I.1,2
2020-03-04
发表期刊NATURE
ISSN0028-0836
EISSN1476-4687
出版年2020
卷号580期号:7802页码:257-+
文章类型Article
语种英语
国家USA
英文关键词

After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.


Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8(+) T cells(1-3). Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name ' mature DCs enriched in immunoregulatory molecules' (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-gamma and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.


领域地球科学 ; 气候变化 ; 资源环境
收录类别SCI-E
WOS记录号WOS:000521531000002
WOS关键词MODELS
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
引用统计
被引频次:430[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/281110
专题地球科学
资源环境科学
气候变化
作者单位1.Yale Sch Med, Dept Internal Med, New Haven, CT 06510 USA;
2.Yale Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA;
3.Yale Sch Med, Dept Pharmacol, New Haven, CT USA
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GB/T 7714
Perry, Rachel J.,Zhang, Dongyan,Guerra, Mateus T.,et al. A conserved dendritic-cell regulatory program limits antitumour immunity[J]. NATURE,2020,580(7802):257-+.
APA Perry, Rachel J..,Zhang, Dongyan.,Guerra, Mateus T..,Brill, Allison L..,Goedeke, Leigh.,...&Shulman, Gerald I..(2020).A conserved dendritic-cell regulatory program limits antitumour immunity.NATURE,580(7802),257-+.
MLA Perry, Rachel J.,et al."A conserved dendritic-cell regulatory program limits antitumour immunity".NATURE 580.7802(2020):257-+.
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