Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation

Ting Li, Shuhui Jiang, Ying Zhang, Jie Luo, Ming Li, Hengte Ke, Yibin Deng, Tao Yang (), Xiaohui Sun () and Huabing Chen ()
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Ting Li: Soochow University
Shuhui Jiang: Soochow University
Ying Zhang: Soochow University
Jie Luo: Soochow University
Ming Li: Soochow University
Hengte Ke: Soochow University
Yibin Deng: Soochow University
Tao Yang: Soochow University
Xiaohui Sun: Soochow University
Huabing Chen: Soochow University

Nature Communications, 2023, vol. 14, issue 1, 1-25

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-38128-x

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