小狗阅读会员会员
医学顶刊SCI精读工具

扫码登录小狗阅读

阅读SCI医学文献
Document
订阅泛读方向 订阅泛读期刊
  • 我的关注
  • 我的关注
  • {{item.title}}

    按需关注领域/方向,精准获取前沿热点

  • {{item.title}}

    {{item.follow}}人关注

  • {{item.subscribe_count}}人订阅

    IF:{{item.impact_factor}}

    {{item.title}}

A conserved dendritic-cell regulatory program limits antitumour immunity.

保守的树突状细胞调节程序限制抗肿瘤免疫。

  • 影响因子:15.21
  • DOI:10.1038/s41586-020-2134-y
  • 作者列表:"Maier B","Leader AM","Chen ST","Tung N","Chang C","LeBerichel J","Chudnovskiy A","Maskey S","Walker L","Finnigan JP","Kirkling ME","Reizis B","Ghosh S","D'Amore NR","Bhardwaj N","Rothlin CV","Wolf A","Flores R","Marron T","Rahman AH","Kenigsberg E","Brown BD","Merad M
  • 发表时间:2020-04-01
Abstract

: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 cells1-3. 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-γ 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.

摘要

: 检查点阻断疗法改善了癌症治疗,但这种免疫疗法在很大一部分患者中失败。传统的 1 型树突状细胞 (DC1s) 在临床前模型中控制对检查点阻断的反应,并与癌症患者更好的总生存期相关,反映了这些细胞引发CD8 + T cells1-3 反应的特化能力。然而,矛盾的是,DC1s可以在抵抗检查点阻断的肿瘤中发现,表明这些细胞的功能可能在一些病变中改变。在这里,使用单细胞RNA测序在人和小鼠非小细胞肺癌中,我们鉴定了一群树突状细胞 (dc) 由于免疫调节基因 (Cd274 、Pdcd1lg2 和Cd200) 和成熟基因 (Cd40 、Ccr7 和Il12b) 的共表达,我们将其命名为 “富含免疫调节分子的成熟dc” (mregdc)。我们发现mregDC程序在摄取肿瘤抗原时由规范DC1s和DC2s表达。我们进一步发现,mregdc中程序性死亡配体 1 蛋白 (一种关键检查点分子) 的上调是由受体酪氨酸激酶AXL诱导的,而白细胞介素 (IL) 的上调-12 严格依赖于干扰素-γ,并且由IL-4 信号传导负控制。阻断IL-4 增强了携带肿瘤抗原的mregDC1s的IL-12 产生,扩大了肿瘤浸润效应T细胞的池并减少了肿瘤负荷。因此,我们发现了与肿瘤抗原摄取相关的调节模块,其降低了人类和小鼠癌症中的DC1 功能。

关键词:
阅读人数:8人
下载该文献
小狗阅读

帮助医生、学生、科研工作者解决SCI文献找不到、看不懂、阅读效率低的问题。提供领域精准的SCI文献,通过多角度解析提高文献阅读效率,从而使用户获得有价值研究思路。

相关文献
影响因子:1.80
发表时间:2020-01-01
DOI:10.1016/j.athoracsur.2019.04.100
作者列表:["Mammana M","Zuin A","Serra E","Bellini A","Rea F"]

METHODS::Pulmonary artery sling is a rare congenital anomaly of the origin and course of the left pulmonary artery. Patients with this condition typically present with respiratory failure in young infancy, and asymptomatic cases are uncommon. We describe the case of an adult patient with a lung adenocarcinoma of the right upper lobe, extending into the hilum and superior mediastinum, and with a previously unknown pulmonary artery sling anomaly. The local invasiveness of the tumor and the peculiar vascular anatomy contributed to a unique surgical scenario, wherein multiple reconstructive procedures were required.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-15
DOI:10.1002/ijc.32532
作者列表:["Hata A","Nakajima T","Matsusaka K","Fukuyo M","Morimoto J","Yamamoto T","Sakairi Y","Rahmutulla B","Ota S","Wada H","Suzuki H","Matsubara H","Yoshino I","Kaneda A"]

METHODS::Patients with idiopathic pulmonary fibrosis (IPF) have higher risk of developing lung cancer, for example, squamous cell carcinoma (SCC), and show poor prognosis, while the molecular basis has not been fully investigated. Here we conducted DNA methylome analysis of lung SCC using 20 SCC samples with/without IPF, and noncancerous lung tissue samples from smokers/nonsmokers, using Infinium HumanMethylation 450K array. SCC was clustered into low- and high-methylation epigenotypes by hierarchical clustering analysis. Genes hypermethylated in SCC significantly included genes targeted by polycomb repressive complex in embryonic stem cells, and genes associated with Gene Ontology terms, for example, "transcription" and "cell adhesion," while genes hypermethylated specifically in high-methylation subgroup significantly included genes associated with "negative regulation of growth." Low-methylation subgroup significantly correlated with IPF (78%, vs. 17% in high-methylation subgroup, p = 0.04), and the correlation was validated by additional Infinium analysis of SCC samples (n = 44 in total), and data from The Cancer Genome Atlas (n = 390). The correlation between low-methylation subgroup and IPF was further validated by quantitative methylation analysis of marker genes commonly hypermethylated in SCC (HOXA2, HOXA9 and PCDHGB6), and markers specifically hypermethylated in high-methylation subgroup (DLEC1, CFTR, MT1M, CRIP3 and ALDH7A1) in 77 SCC cases using pyrosequencing (p = 0.003). Furthermore, low-methylation epigenotype significantly correlated with poorer prognosis among all SCC patients, or among patients without IPF. Multivariate analysis showed that low-methylation epigenotype is an independent predictor of poor prognosis. These may suggest that lung SCC could be stratified into molecular subtypes with distinct prognosis, and low-methylation lung SCC that significantly correlates with IPF shows unfavorable outcome.

翻译标题与摘要 下载文献
影响因子:6.93
发表时间:2020-01-01
DOI:10.1002/ijc.32530
作者列表:["Zhang L","Yang Y","Chai L","Bu H","Yang Y","Huang H","Ran J","Zhu Y","Li L","Chen F","Li W"]

METHODS::The role of Fyn-related kinase (FRK) in malignant tumors remains controversial. Our study investigated the function of FRK in lung cancer. Immunohistochemistry staining and generating a knockout of FRK by CRISPR/Cas9 in H1299 (FRK-KO-H1299) cells were strategies used to explore the role of FRK. Immunohistochemistry staining indicated that FRK expression was elevated in 223 lung cancer tissues compared to 26 distant normal lung tissues. FRK contributed to poor survival status in lung cancer patients and acted as a predictor for poor prognosis of lung cancer. Knockout of FRK by CRISPR/Cas9 markedly inhibited proliferation, invasion, colony formation and epithelial-mesenchymal transition (EMT) process in the lung cancer cell line H1299. Further exploration indicated that FRK-KO damaged the stemness phenotype of H1299 by inhibiting CD44 and CD133 expression. Seahorse detection and a U-13 C flux assay revealed that FRK-KO induced metabolism reprogramming by inhibiting the Warburg effect and changing the energy type in H1299 cells. Epidermal growth factor stimulation recovered the expression of FRK and biological functions, metabolic reprogramming and stemness phenotype of H1299 cells. FRK plays an oncogenic role in lung cancer cells via a novel regulation mechanism of enhancing the stemness of H1299 cells by inducing metabolism reprogramming, which finally promotes EMT and metastasis. Our study also indicates that FRK could be used as a potential therapeutic target for drug development.

翻译标题与摘要 下载文献
肺肿瘤方向

肺肿瘤,又叫支气管肺癌,是常见的恶性肿瘤之一。肺肿瘤的治疗为包括手术、中药、放疗、化疗及免疫等多学科的综合治疗。

复制标题
发送后即可在该邮箱或我的下载查看该文献
发送
该文献默认存储到我的下载

科研福利

报名咨询

建议反馈
问题标题:
联系方式:
电子邮件:
您的需求: