TGF-β1-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model.
Fang HuangJiangbo WanSiguo HaoXiaohui DengLinjun ChenLiyuan MaPublished in: Cancer immunology, immunotherapy : CII (2017)
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function. In addition, DC pulsed with LEXTGF-β1si (DCLEX-TGF-β1si) more effectively promoted CD4+ T cell proliferation in vitro and Th1 cytokine secretion and induced tumor-specific CTL response. This response was higher in potency compared to that noted by the other two formulations. Moreover, DCLEX-TGF-β1si inhibited tumor growth more efficiently than other formulations did as the preventive or therapeutic tumor vaccine. Accordingly, these findings revealed that DCLEX-TGF-β1si induced a more potent antigen-specific anti-leukemic immunity than DC pulsed with exosomes from non-manipulated L1210 cells. This indicated that the targeting of DC by LEXTGF-β1si may be used as a promising approach for leukemia immunotherapy.
Keyphrases
- dendritic cells
- transforming growth factor
- immune response
- room temperature
- induced apoptosis
- mesenchymal stem cells
- acute myeloid leukemia
- stem cells
- cell cycle arrest
- clinical trial
- regulatory t cells
- cell proliferation
- mouse model
- epithelial mesenchymal transition
- bone marrow
- poor prognosis
- high glucose
- randomized controlled trial
- cell death
- drug delivery
- pi k akt
- endothelial cells
- long non coding rna
- toll like receptor
- artificial intelligence
- drug induced
- single cell
- ionic liquid
- big data
- single molecule