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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
OPN 通过 p65/c-Myc/CD155 轴抑制 CD8+ T 细胞浸润和活化，促进肝细胞癌进展
英文原题：OPN Promotes Hepatocellular Carcinoma Progression Through the p65/c-Myc/CD155 Axis by Suppressing CD8+ T Cell Infiltration and Activation.
查看英文原题
OPN Promotes Hepatocellular Carcinoma Progression Through the p65/c-Myc/CD155 Axis by Suppressing CD8+ T Cell Infiltration and Activation.
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研究概要
OPN 通过 NF-κB (p65)/c-Myc/CD155 轴抑制 CD8+ T 细胞免疫，驱动 HCC 进展。靶向该通路可能增强抗肿瘤免疫，是 HCC 有前景的治疗策略。
研究思路结论见上方概要
背景
肝细胞癌（HCC）的免疫抑制微环境由多条致癌通路塑造，但骨桥蛋白（OPN）——一种在HCC中频繁过表达的分子——如何调控抗肿瘤免疫仍不清楚。
方法
明确OPN调控HCC免疫微环境的机制，重点探讨其对CD155的调控及其对CD8+ T细胞介导的抗肿瘤应答的影响。
结果
我们发现OPN激活p65/NF-κB - c-Myc/CD155信号轴，导致CD155显著上调以及瘤内CD8+ T细胞浸润和效应活性受损。这些免疫抑制效应独立于肿瘤干性标志物变化或Treg积聚而发生。p65的基因抑制消除了OPN诱导的CD155表达，并在体内减轻了肿瘤进展，证明了该通路的功能必要性。
展开英文摘要原文
METHODS
To define the mechanism by which OPN modulates the HCC immune microenvironment, with a focus on its regulation of CD155 and its impact on CD8 + T-cell - mediated anti-tumor responses.
RESULTS
We identified that OPN activates the p65/NF-κB - c-Myc/CD155 signaling axis, leading to robust upregulation of CD155 and impaired intratumoral CD8 + T-cell infiltration and effector activity. These immunosuppressive effects occurred independently of changes in tumor stemness markers or Treg accumulation. Genetic suppression of p65 abrogated OPN-induced CD155 expression and mitigated tumor progression in vivo, demonstrating the pathway's functional requirement. DISCUSSION: OPN drives HCC progression by suppressing CD8 + T-cell immunity through the NF-κB (p65)/c-Myc/CD155 axis. Targeting this pathway may enhance anti-tumor immunity and represents a promising therapeutic strategy for HCC.
论文信息
- 作者
- Fang J、Liu L、He Z、Ling M、Liang J、Lei Y、Wen Z、Guo J
- 单位
- Department of Tumor Hematology, Affiliated Hospital Group of Guangdong Medical University Panyu He Xian Memorial Hospital/Panyu Women and Children's Medical Center, Guangdong Medical University (Guangzhou Panyu District Maternal and Child Health Hospital), Guangzhou, China.China
- 期刊
- Immunological investigations2026 Feb
- 原文标识
- PubMed 41416769 · DOI 10.1080/08820139.2025.2599834