PD-1hi Identifies a Novel Regulatory B-cell Population in Human Hepatoma That Promotes Disease Progression

下调和上调 调节性B细胞 白细胞介素10 癌症研究 生物 细胞 人口 免疫学 B细胞 免疫系统 癌症 医学 基因 抗体 遗传学 环境卫生
作者
Christos Xiao,Xiang‐Ming Lao,Minmin Chen,Ruixian Liu,Wei Yuan,Fang‐Zhu Ouyang,Dong‐Ping Chen,Xiaoyu Zhao,Qiyi Zhao,Xuefeng Li,Chuan-Lu Liu,Limin Zheng,Dong‐Ming Kuang
出处
期刊:Cancer Discovery [American Association for Cancer Research]
卷期号:6 (5): 546-559 被引量:325
标识
DOI:10.1158/2159-8290.cd-15-1408
摘要

Abstract B cells often constitute abundant cellular components in human tumors. Regulatory B cells that are functionally defined by their ability to produce IL10 downregulate inflammation and control T-cell immunity. Here, we identified a protumorigenic subset of B cells that constitutively expressed higher levels of programmed cell death-1 (PD-1) and constituted ∼10% of all B cells in advanced-stage hepatocellular carcinoma (HCC). These PD-1hi B cells exhibited a unique CD5hiCD24−/+CD27hi/+CD38dim phenotype different from the phenotype of conventional CD24hiCD38hi peripheral regulatory B cells. TLR4-mediated BCL6 upregulation was crucial for PD-1hi B-cell induction by HCC environmental factors, and that effect was abolished by IL4-elicited STAT6 phosphorylation. Importantly, upon encountering PD-L1+ cells or undergoing PD-1 triggering, PD-1hi B cells acquired regulatory functions that suppressed tumor-specific T-cell immunity and promoted cancer growth via IL10 signals. Our findings provide significant new insights for human cancer immunosuppression and anticancer therapies regarding PD-1/PD-L1. Significance: We identify a novel protumorigenic PD-1hi B-cell subset in human HCC that exhibits a phenotype distinct from that of peripheral regulatory B cells. TLR4-mediated BCL6 upregulation is critical for induction of PD-1hi B cells, which operate via IL10-dependent pathways upon interacting with PD-L1 to cause T-cell dysfunction and foster disease progression. Cancer Discov; 6(5); 546–59. ©2016 AACR. See related commentary by Ren et al., p. 477. This article is highlighted in the In This Issue feature, p. 461
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
adam完成签到,获得积分10
刚刚
狂野书易完成签到,获得积分10
刚刚
2秒前
浮游应助依于采纳,获得10
2秒前
脑洞疼应助科研通管家采纳,获得10
2秒前
星辰大海应助科研通管家采纳,获得10
2秒前
gkads应助科研通管家采纳,获得10
2秒前
浮游应助科研通管家采纳,获得10
2秒前
CodeCraft应助科研通管家采纳,获得10
2秒前
ding应助科研通管家采纳,获得10
2秒前
3秒前
3秒前
3秒前
科研通AI6应助发文章12138采纳,获得10
3秒前
郭丹丹完成签到 ,获得积分10
5秒前
6秒前
liu完成签到,获得积分10
7秒前
树野完成签到,获得积分10
8秒前
灵主完成签到,获得积分10
8秒前
8秒前
JERRY发布了新的文献求助10
10秒前
11秒前
酸奶巧克力完成签到,获得积分10
11秒前
11秒前
DJsky123发布了新的文献求助10
12秒前
kk完成签到 ,获得积分10
13秒前
单纯乘风发布了新的文献求助10
13秒前
Queenie发布了新的文献求助30
13秒前
THREE完成签到 ,获得积分10
13秒前
小梦完成签到,获得积分10
14秒前
冷酷的海露完成签到,获得积分20
15秒前
王帅关注了科研通微信公众号
15秒前
ATOM完成签到,获得积分10
15秒前
17秒前
ATOM发布了新的文献求助50
18秒前
harry2021完成签到,获得积分10
19秒前
领导范儿应助lxy采纳,获得10
19秒前
orixero应助岸久舞若衣采纳,获得10
19秒前
19秒前
梁平发布了新的文献求助10
21秒前
高分求助中
Encyclopedia of Quaternary Science Third edition 2025 12000
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
The Social Work Ethics Casebook: Cases and Commentary (revised 2nd ed.). Frederic G. Reamer 800
Beyond the sentence : discourse and sentential form / edited by Jessica R. Wirth 600
Holistic Discourse Analysis 600
Vertébrés continentaux du Crétacé supérieur de Provence (Sud-Est de la France) 600
Reliability Monitoring Program 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 物理化学 基因 遗传学 催化作用 冶金 量子力学 光电子学
热门帖子
关注 科研通微信公众号,转发送积分 5339366
求助须知:如何正确求助?哪些是违规求助? 4476236
关于积分的说明 13930768
捐赠科研通 4371637
什么是DOI,文献DOI怎么找? 2402047
邀请新用户注册赠送积分活动 1394975
关于科研通互助平台的介绍 1366898