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

Author

Listed:
  • 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
    Soochow University)

  • Xiaohui Sun

    (Soochow University)

  • Huabing Chen

    (Soochow University
    Soochow University)

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.

Suggested Citation

  • Ting Li & Shuhui Jiang & Ying Zhang & Jie Luo & Ming Li & Hengte Ke & Yibin Deng & Tao Yang & Xiaohui Sun & Huabing Chen, 2023. "Nanoparticle-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38128-x
    DOI: 10.1038/s41467-023-38128-x
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    References listed on IDEAS

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    1. Sushrut Kamerkar & Valerie S. LeBleu & Hikaru Sugimoto & Sujuan Yang & Carolina F. Ruivo & Sonia A. Melo & J. Jack Lee & Raghu Kalluri, 2017. "Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer," Nature, Nature, vol. 546(7659), pages 498-503, June.
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    1. Lin Li & Mengxing Zhang & Jing Li & Tiantian Liu & Qixue Bao & Xi Li & Jiaying Long & Leyao Fu & Zhirong Zhang & Shiqi Huang & Zhenmi Liu & Ling Zhang, 2023. "Cholesterol removal improves performance of a model biomimetic system to co-deliver a photothermal agent and a STING agonist for cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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