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Tumor-derived exosome-based microRNA-206 delivery system as dual modulators of the immune microenvironment and gut
Jinhua Tian1, Miao Liu1, Xiaojuan Yang2
1School of Inspection, Ningxia Medical University, Yinchuan 750004, China; The First School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, China.
Abstract:
Immune checkpoint blockade (ICB) holds significant therapeutic potential for colorectal cancer (CRC). However, its clinical efficacy remains limited by relatively low response rates. Recent studies suggest that combining microRNAs (miRNAs) with immune checkpoint blockade offers a promising strategy for enhancing CRC treatment outcomes. In our previous work, we found that miRNA-206 (miR206), a small non-coding RNA, effectively inhibited tumor growth by targeting T cell immune receptor with immunoglobulin and ITIM domain (TIGIT). Nevertheless, how miR206 contributes to the modulation of the immune microenvironment and whether it influences gut microbiota composition remain unclear. Herein, we proposed an engineered exosome delivery system consisting of extracellular vesicles derived from miR206-overexpressing tumor cells (LV-miR206-HT29-EXO) to enhance CRC immunotherapy. The engineered exosome facilitated the efficient delivery of miR206 to tumor sites. In vitro and in vivo studies demonstrated that LV-miR206-HT29-EXO significantly inhibited tumor growth, migration, and invasion while promoting tumor apoptosis. Notably, the engineered nanoplatform also exhibited substantial antitumor efficacy in CRC mice models by modulating interactions among tumor cells, the gut microbiota, and the immune microenvironment. These findings highlighted the potential of tumor-derived exosome-based miRNA delivery system for CRC immunotherapy.
Insights
Engineered exosomes delivering miRNA-206 (miR206) show promise for colorectal cancer (CRC) immunotherapy by targeting TIGIT. This novel approach enhances immune response and inhibits tumor progression in preclinical models.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
- Nanotechnology
Background:
- Immune checkpoint blockade (ICB) has therapeutic potential for colorectal cancer (CRC), but response rates are limited.
- MicroRNAs (miRNAs) combined with ICB may enhance CRC treatment.
- miRNA-206 (miR206) inhibits tumor growth by targeting TIGIT, but its role in the immune microenvironment and gut microbiota is unclear.
Purpose of the Study:
- To develop an engineered exosome delivery system for miR206 to enhance CRC immunotherapy.
- To investigate the antitumor efficacy and mechanisms of miR206-loaded exosomes in CRC.
Main Methods:
- Engineered exosomes (LV-miR206-HT29-EXO) derived from miR206-overexpressing tumor cells were created.
- In vitro and in vivo studies were conducted using CRC models.
- Tumor growth, migration, invasion, apoptosis, immune microenvironment, and gut microbiota were analyzed.
Main Results:
- LV-miR206-HT29-EXO efficiently delivered miR206 to tumor sites.
- The engineered exosomes significantly inhibited CRC tumor growth, migration, and invasion while promoting apoptosis.
- The nanoplatform demonstrated antitumor efficacy by modulating tumor cells, gut microbiota, and the immune microenvironment in CRC mice.
Conclusions:
- Engineered exosomes serve as an effective delivery system for miR206 in CRC immunotherapy.
- This approach modulates the tumor microenvironment and gut microbiota, leading to enhanced antitumor effects.
- Tumor-derived exosome-based miRNA delivery holds significant potential for improving CRC treatment outcomes.
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