基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
PARP 和 WEE1 联合抑制在 BRCA1/2 野生型三阴性乳腺癌中触发抗肿瘤免疫应答
英文原题：Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer.
查看英文原题
Combined PARP and WEE1 inhibition triggers anti-tumor immune response in BRCA1/2 wildtype triple-negative breast cancer.
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中文摘要
治疗三阴性乳腺癌（TNBC）需要能够与免疫疗法有效联合的新策略。我们发现，在 BRCA1/2 野生型 TNBC 临床前模型中，联合抑制 PARP 和 WEE1 可协同控制肿瘤生长。PARP 抑制剂（PARPi）olaparib 与 WEE1 抑制剂（WEE1i）adavosertib 联用可增强抗肿瘤免疫反应，包括激活 STING 通路。在 BRCA1/2 野生型 TNBC 小鼠肿瘤模型中，加入 STING 激动剂后，持久性肿瘤消退进一步改善，生存结局也显著提升。此外，我们发现基线TIL（肿瘤浸润淋巴细胞）水平可能是 BRCA1/2 野生型 TNBC 对 PARPi、WEE1i 及免疫疗法产生应答的预测性生物标志物。
展开英文摘要原文
Novel therapeutic strategies that can effectively combine with immunotherapies are needed in the treatment of triple-negative breast cancer (TNBC).
We demonstrate that combined PARP and WEE1 inhibition are synergistic in controlling tumour growth in BRCA1/2 wild-type TNBC preclinical models. The PARP inhibitor (PARPi) olaparib combined with the WEE1 inhibitor (WEE1i) adavosertib triggered increases in anti-tumour immune responses, including STING pathway activation. Combinations with a STING agonist resulted in further improved durable tumour regression and significant improvements in survival outcomes in murine tumour models of BRCA1/2 wild-type TNBC.
In addition, we have identified baseline tumour-infiltrating lymphocyte (TIL) levels as a potential predictive biomarker of response to PARPi, WEE1i and immunotherapies in BRCA1/2 wild-type TNBC.
论文信息
- 作者
- Teo ZL、O'Connor MJ、Versaci S、Clarke KA、Brown ER、Percy LW、Kuykhoven K、Mintoff CP
- 第一作者单位
- Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia.Australia
- 通讯作者单位
- Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC, 3000, Australia. sherene.loi@petermac.org.Australia
- 期刊
- NPJ breast cancer2023 Aug 15
- 原文标识
- PubMed 37582853 · DOI 10.1038/s41523-023-00568-5
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