亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

HMGB3 Contributes to Anti‐PD‐1 Resistance by Inhibiting IFN‐γ‐Driven Ferroptosis in TNBC

生物 癌症研究 癌细胞 STAT1 癌症 干扰素 免疫学 遗传学
作者
Bo Luo,Hongmei Zheng,Gai Liang,Yan Luo,Qu Zhang,Xiang Li
出处
期刊:Molecular Carcinogenesis [Wiley]
被引量:2
标识
DOI:10.1002/mc.23861
摘要

Our previous studies showed HMGB3 expression may correlate with immunotherapy efficacy in breast cancer patients. Here, we investigated whether HMGB3 overexpression has an impact on anti-PD-1 therapy in triple-negative breast cancer (TNBC) and its molecular mechanisms. Animal models were established to observe the effect of HMGB3 on sensitivity to anti-PD-1 treatment. Correlation of HMGB3 expression and ferroptosis preventive proteins in TNBC patients' tissues with anti-PD-1 therapy efficacy was analyzed. The impact of HMGB3 on IFN-γ (Interferon-gamma) inhibitory effects and signaling was examined in human TNBC cells where HMGB3 expression was knocked down using siRNA. Moreover, TNBC cells stably transfected with lentiviral vectors containing cDNA of HMGB3 were also used to confirm the effect of overexpression of HMGB3 on IFN-γ inhibitory effect and signaling. Effect of HMGB3 on IFN-γ-driven ferroptosis and ferroptosis-associated protein expression were also investigated. Correlation of HMGB3 and IRF1 and GPX4 expression in patient's cancer tissue were also investigated. Our results demonstrated that HMGB3 expression contributes to resistance to anti-PD-1 therapy in vivo. HMGB3 expression correlated with treatment efficacy of immunotherapy and survival in TNBC patients. HMGB3 silence decreased resistance of breast cancer cells to IFN-γ cytotoxic effect, while HMGB3 overexpression increased resistance of these cancer cells. HMGB3 silence increased STAT1 phosphorylation and IRF1 expression upon IFN-γ treatment compared with control. Overexpression of HMGB3 inhibited STAT1 phosphorylation and IFN-γ signaling in TNBC cells. Moreover, HMGB3 also increased STAT3 activation and had an effect of interaction between STAT1 and STAT3. HMGB3 overexpression decreased IFN-γ-driven ferroptosis in TNBC cells. HMGB3 increased ferroptosis-inhibitory proteins (SLC7A11, GPX4, and SLC3A2) expression in TNBC cells. Ferroptosis inhibition recovers resistance to anti-PD-1 therapy in vivo. Immunohistochemistry showed HMGB3 expression correlated with ferroptosis-associated proteins and IRF1 expression in breast cancer tissue. HMGB3 contributes to anti-PD-1 resistance by inhibiting IFN-γ-driven ferroptosis in TNBC which suggested HMGB3 is a potential co-target with anti-PD-1 therapy for TNBC.
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
rumengren完成签到 ,获得积分10
24秒前
37秒前
嘉嘉完成签到 ,获得积分10
42秒前
重要元灵完成签到 ,获得积分10
1分钟前
科研通AI2S应助科研通管家采纳,获得10
1分钟前
完美世界应助科研通管家采纳,获得10
1分钟前
俏皮元珊完成签到 ,获得积分10
1分钟前
21完成签到 ,获得积分10
2分钟前
2分钟前
自然芷文发布了新的文献求助10
2分钟前
112345完成签到 ,获得积分10
2分钟前
自然芷文完成签到,获得积分10
3分钟前
3分钟前
迷人问兰发布了新的文献求助10
3分钟前
科研通AI2S应助科研通管家采纳,获得19
3分钟前
sjyu1985完成签到 ,获得积分10
4分钟前
闻巷雨完成签到 ,获得积分10
4分钟前
pegasus0802完成签到 ,获得积分10
4分钟前
5823364完成签到,获得积分10
5分钟前
automan完成签到,获得积分10
5分钟前
天亮polar完成签到,获得积分10
5分钟前
5分钟前
5分钟前
6分钟前
朴实云应发布了新的文献求助10
6分钟前
林子青完成签到,获得积分10
6分钟前
核桃发布了新的文献求助30
6分钟前
李健应助reerwt采纳,获得10
7分钟前
7分钟前
ICSSCI发布了新的文献求助10
7分钟前
7分钟前
刘宇童给刘宇童的求助进行了留言
7分钟前
reerwt发布了新的文献求助10
7分钟前
7分钟前
科研通AI2S应助科研通管家采纳,获得10
7分钟前
科研通AI2S应助科研通管家采纳,获得10
7分钟前
ICSSCI完成签到,获得积分10
7分钟前
7分钟前
董可以发布了新的文献求助10
8分钟前
风华正茂完成签到,获得积分10
8分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990049
求助须知:如何正确求助?哪些是违规求助? 3532108
关于积分的说明 11256369
捐赠科研通 3270998
什么是DOI,文献DOI怎么找? 1805166
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809228