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Published on: September 12, 2019
Manipulating Liver Bile Acid Signaling by Nanodelivery of Bile Acid Receptor Modulators for Liver Cancer
Guofeng Ji1,2, Xinghui Si1,3, Si Dong4
1Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Abstract:
Gut bacteria and their metabolites influence the immune microenvironment of liver through the gut-liver axis, thus representing emerging therapeutic targets for liver cancer therapy. However, directly manipulating gut microbiota or their metabolites is not practical in clinic since the safety concerns and the complicated mechanism of action. Considering the dysregulated bile acid profiles associated with liver cancer, here we propose a strategy that directly manipulates the primary and secondary bile acid receptors through nanoapproach as an alternative and more precise way for liver cancer therapy. We show that nanodelivery of bile acid receptor modulators elicited robust antitumor immune responses and significantly changed the immune microenvironment in the murine hepatic tumor. In addition, ex vivo stimulation on both murine and patient hepatic tumor tissues suggests the observation here may be meaningful for clinical practice. This study elucidates a novel and precise strategy for liver cancer immunotherapy.
Insights
This study introduces a novel nanodelivery approach to precisely target bile acid receptors, enhancing immunotherapy for liver cancer. This method stimulates antitumor immune responses and modifies the liver tumor microenvironment.
Area of Science:
- Immunology
- Hepatology
- Nanotechnology
Background:
- Gut bacteria and metabolites impact liver cancer via the gut-liver axis.
- Directly manipulating gut microbiota is clinically challenging due to safety and complexity.
- Altered bile acid profiles are linked to liver cancer, suggesting them as therapeutic targets.
Purpose of the Study:
- To develop a precise nanodelivery strategy for modulating bile acid receptors.
- To investigate the therapeutic potential of targeting bile acid receptors for liver cancer immunotherapy.
- To evaluate the impact of this approach on the liver tumor immune microenvironment.
Main Methods:
- Nanodelivery of bile acid receptor modulators in a murine hepatic tumor model.
- Analysis of immune microenvironment changes in response to treatment.
- Ex vivo stimulation assays using murine and patient hepatic tumor tissues.
Main Results:
- Nanodelivery of modulators elicited significant antitumor immune responses.
- The immune microenvironment of murine hepatic tumors was demonstrably altered.
- Ex vivo results indicate potential clinical relevance for patient treatment.
Conclusions:
- Directly targeting bile acid receptors via nanodelivery offers a precise strategy for liver cancer immunotherapy.
- This approach represents a promising alternative to direct gut microbiota manipulation.
- Findings suggest potential clinical applicability in treating liver cancer.
