高铁F1
封锁
癌症研究
TRPV1型
免疫疗法
热休克蛋白
癌症免疫疗法
免疫检查点
免疫系统
医学
瞬时受体电位通道
化学
热休克蛋白70
免疫学
受体
内科学
生物化学
基因
作者
Ting Li,Shuhui Jiang,Ying Zhang,Jie Luo,Ming Li,Hengte Ke,Yibin Deng,Tao Yang,Xiaohui Sun,Huabing Chen
标识
DOI:10.1038/s41467-023-38128-x
摘要
The survival of malignant tumors is highly dependent on their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy. However, precisely dismantling self-defenses to amplify antitumor potency remains unexplored. Herein, we demonstrate that nanoparticle-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade potentiates thermo-immunotherapy via suppressing heat shock factor 1 (HSF1)-mediated dual self-defense pathways. TRPV1 blockade inhibits hyperthermia-induced calcium influx and subsequent nuclear translocation of HSF1, which selectively suppresses stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumor models. Particularly, the suppression of HSF1 translocation further restrains the transforming growth factor β (TGFβ) pathway to degrade the tumor stroma, which improves the infiltration of antitumor therapeutics (e.g. anti-PD-L1 antibody) and immune cells into highly fibrotic and immunosuppressive pancreatic cancers. As a result, TRPV1 blockade retrieves thermo-immunotherapy with tumor-eradicable and immune memory effects. The nanoparticle-mediated TRPV1 blockade represents as an effective approach to dismantle self-defenses for potent cancer therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI