Intrahepatic immunoglobulin a complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of hepatocellular carcinoma

肝细胞癌 肿瘤微环境 成纤维细胞活化蛋白 抗体 癌症研究 CD8型 流式细胞术 细胞毒性T细胞 医学 肿瘤进展 癌相关成纤维细胞 免疫球蛋白A 免疫系统 免疫球蛋白G 内科学 生物 癌症 免疫学 体外 生物化学
作者
Jong Geun Park,Pu Reun Roh,Min Woo Kang,Sung Woo Cho,Suhyun Hwangbo,Hae Deok Jung,Hyun Uk Kim,Ji Hoon Kim,Jae-Sung Yoo,Ji Won Han,Jeong Won Jang,Jong Young Choi,Seung Kew Yoon,Young Kyoung You,Ho Joong Choi,Jae Yong Ryu,Pil Soo Sung
出处
期刊:Hepatology [Wiley]
被引量:3
标识
DOI:10.1097/hep.0000000000000772
摘要

Background and Aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment (TME). Immunoglobulin A (IgA) contributes to inflammation and dismantling anti-tumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in the TME of hepatocellular carcinoma (HCC). Approach and Results: CAF dynamics in HCC TME were analyzed via single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro . Progression-free survival of advanced HCC patients treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that sub-cluster proportions in the CAF-fibroblast activation protein-α (FAP) matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of FAP in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 (PD-L1) expression levels than those in mock-treated CAFs ( p <0.05). Co-culture with CAFs attenuated cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells co-cultured with IgA-treated CAFs exhibited increased programmed death-1 (PD-1) expression levels than those co-cultured with mock-treated CAFs ( p <0.05). Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T cell function. Our study highlighted their potential roles in tumor progression and immune suppression.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
青鸟飞鱼完成签到,获得积分10
刚刚
沐阳发布了新的文献求助10
1秒前
呆萌谷兰完成签到,获得积分20
2秒前
changl2023完成签到,获得积分10
2秒前
zs1234发布了新的文献求助10
2秒前
Gezelligheid.发布了新的文献求助10
2秒前
2秒前
李健应助dddd采纳,获得10
3秒前
问问大哥完成签到,获得积分10
3秒前
机灵鸡应助xzz采纳,获得20
5秒前
5秒前
5秒前
赘婿应助我爱科研111采纳,获得10
6秒前
redondo完成签到,获得积分10
6秒前
6秒前
Arthur Zhu完成签到,获得积分10
7秒前
科研肥料完成签到,获得积分10
7秒前
顾矜应助Lee采纳,获得10
7秒前
科目三应助Rain采纳,获得10
8秒前
deng-deng完成签到,获得积分10
8秒前
任性的秋蝶完成签到,获得积分10
9秒前
费梦山完成签到,获得积分10
9秒前
9秒前
10秒前
10秒前
10秒前
坚强的依秋完成签到,获得积分10
10秒前
YonghuanChen发布了新的文献求助10
11秒前
11秒前
英勇的雁发布了新的文献求助10
11秒前
Gezelligheid.完成签到,获得积分20
12秒前
spencer177完成签到,获得积分10
12秒前
故意的问安完成签到 ,获得积分10
12秒前
早睡早起身体棒完成签到,获得积分10
12秒前
Susie完成签到,获得积分10
13秒前
和谐小霸王完成签到 ,获得积分10
13秒前
爱笑的蘑菇完成签到,获得积分10
13秒前
张杰完成签到,获得积分10
13秒前
朴实的凝雁完成签到,获得积分20
13秒前
13秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Foreign Policy of the French Second Empire: A Bibliography 500
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3147058
求助须知:如何正确求助?哪些是违规求助? 2798385
关于积分的说明 7828457
捐赠科研通 2454989
什么是DOI,文献DOI怎么找? 1306573
科研通“疑难数据库(出版商)”最低求助积分说明 627831
版权声明 601565