PROTAC 工程化蛋白/DNA 纳米抗原是癌症免疫治疗中树突状细胞疫苗的有效增强剂
PROTAC-Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向肿瘤相关树突状细胞中的 WEE1 通过 cGAS/STING 通路增强抗肿瘤免疫
英文原题：Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway.
查看英文原题
Targeting WEE1 in tumor-associated dendritic cells potentiates antitumor immunity via the cGAS/STING pathway.
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中文摘要
DNA损伤深刻影响癌症进展和免疫细胞功能。虽然研究主要集中在肿瘤细胞上，但DNA损伤对免疫细胞的影响仍研究不足。在这里，我们观察到肿瘤相关树突状细胞（TADC）中存在显著的DNA损伤，并伴有丝氨酸/苏氨酸激酶WEE1的上调，WEE1是DNA损伤修复的关键调节因子。有趣的是，DNA损伤也刺激DC活化。WEE1抑制通过cGAS/STING通路激活TADC，增加IL-12和I型干扰素表达，从而增强抗肿瘤免疫反应并改善肿瘤控制。此外，WEE1抑制增强了DC疫苗的疗效，并与免疫检查点阻断治疗产生协同作用。这些发现突出了WEE1信号在肿瘤微环境中DC的DNA损伤修复中的关键作用，进而抑制抗肿瘤免疫反应。因此，靶向DC中的WEE1代表了一种有前景的方法，可增强T细胞活化并提高癌症免疫治疗的有效性。
展开英文摘要原文
DNA damage profoundly affects cancer progression and immune cell function. While research primarily focuses on tumor cells, the effects of DNA damage on immune cells remain understudied.
Here, we observe significant DNA damage in tumor-associated dendritic cells (TADCs), accompanied by the upregulation of the serine/threonine kinase WEE1, a crucial regulator of DNA damage repair. Interestingly, DNA damage also stimulates DC activation. WEE1 inhibition activates TADCs through the cGAS/STING pathway, increasing IL-12 and type I interferon expression, thus enhancing the antitumor immune response and improving tumor control.
Additionally, WEE1 inhibition augments the efficacy of DC vaccines and synergizes with immune checkpoint blockade therapy.
These findings highlight a pivotal role of WEE1 signaling in DNA damage repair in DCs within the tumor microenvironment, which in turn suppresses the antitumor immune response.
Therefore, targeting WEE1 in DCs represents a promising approach to enhance T cell activation and improve the effectiveness of cancer immunotherapy.
论文信息
- 作者
- Ng II、Zhang Z、Xiao K、Ye M、Tian T、Zhu Y、He Y、Chu L
- 第一作者单位
- State Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China.China
- 通讯作者单位
- State Key Laboratory of Molecular Oncology, School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China. Electronic address: hdtang@tsinghua.edu.cn.China
- 期刊
- Cell reports2025 Jun 24
- 原文标识
- PubMed 40397571 · DOI 10.1016/j.celrep.2025.115733