RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
TREX1，治疗 MSI-H 肿瘤的捕食者？
英文原题：TREX1, a predator for treating MSI-H tumors?
查看英文原题
TREX1, a predator for treating MSI-H tumors?
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中文摘要
免疫治疗已经彻底改变了癌症治疗；然而，一部分微卫星高度不稳定（MSI-H）肿瘤患者尽管具有升高的肿瘤突变负荷和免疫原性潜力，仍对治疗无应答。在最近的一项研究中，Xu等人揭示了MSI-H肿瘤中由核酸外切酶TREX1介导的一种关键免疫逃逸机制，TREX1降解胞质DNA并抑制环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子（cGAS-STING）-I型干扰素通路的激活。TREX1缺失可恢复胞质DNA感知，促进CD8+ T细胞和NK细胞浸润，并增强抗肿瘤免疫。这些发现凸显TREX1作为克服免疫检查点阻断耐药的潜在治疗靶点。
展开英文摘要原文
Immunotherapy has revolutionized cancer treatment; yet, a subset of patients with microsatellite instability-high (MSI-H) tumors fails to respond to treatment despite their elevated tumor mutational burden and immunogenic potential. In a recent study, Xu et al.
uncover a key mechanism of immune evasion in MSI-H tumors mediated by the exonuclease TREX1, which degrades cytosolic DNA and suppresses activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING)-type I interferon pathway. Loss of TREX1 restores cytosolic DNA sensing, promotes CD8 + T and NK cell infiltration, and enhances antitumor immunity.
These findings highlight TREX1 as a potential therapeutic target to overcome resistance to immune checkpoint blockade.
论文信息
- 作者
- Benidovskaya E、Deneft J、Van den Eynde M
- 单位
- IREC MIRO-ONCO, Laboratory of Oncology, UCLouvain, Brussels, Belgium.Belgium
- 期刊
- Molecular oncology2026 Feb
- 原文标识
- PubMed 41288129 · DOI 10.1002/1878-0261.70173
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