Journal
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume 14, Issue 10, Pages 1826-1835Publisher
AMER SCIENTIFIC PUBLISHERS
DOI: 10.1166/jbn.2018.2616
Keywords
Dendritic Cell; Cancer-Associated Fibroblasts; Fusion Cell; Cytotoxic T Lymphocytes; Microenvironment; Nanomaterial
Funding
- Project of National Natural Scientific Foundation of China [81773254, 81560494]
- Programs for Changjiang Scholars and Innovative Research Team in University [IRT_15R13]
- International Cooperation Project of the Misnistry of Science and Technology of China [2015DFA31320]
- Post-doctoral Science Foundation funded project of Guangxi Medical University [02306214010D]
- Project for Innovative Research Team in Guangxi Natural Science Foundation [2015GXNSFFA139001]
- project for International Nanobody Research Center of Guangxi [GuiKe-AD17195001]
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Here we explored the fusion of dendritic cells (DCs), potent antigen-presenting cells that initiate primary immune responses, with cancer-associated fibroblasts (CAFs), which are a stromal component needed for tumor progression, with the aim of stimulating T cells to inhibit tumor growth. Dendritic cells from the bone marrow of BALB/c mice were co-cultured with CAFs from H22 mouse hepatoma cells. CAFs were found to express fibroblast activation protein and alpha-smooth muscle actin by flow cytometry, Western blotting and immunofluorescence. Polyethylene glycol was added to the co-culture medium to encourage fusion, and the ability of the resulting fusion cells to produce TNF-alpha, IL-1 beta, IL-6, and IL-12p70 was confirmed using ELISA. These fusion cells efficiently stimulated T lymphocytes in vitro, causing them to generate IFN-alpha and IFN-gamma. T cells activated by DC/CAF fusion cells led to strong CTL response against CAFs in vitro. The activated T cells also inhibited growth of H22 xenografts in vivo. These results indicate that DC/CAF fusion cells show potential for stimulating T cells as a novel anti-tumor vaccine.
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