The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector |
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Authors: | Rilun Li Heng Hu Huiying Ma Long Chen Shuang Zhou Binbin Liu Yinkun Liu Chunmin Liang |
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Institution: | 1. Department of Anatomy and Histology & Embryology, Shanghai Medical College of Fudan University, 138 Yixueyuan Road, Shanghai, 200032, People’s Republic of China 2. Liver Cancer Institute of Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China
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Abstract: | To explore the anti-tumor effect and immune mechanism mediated by a new recombinant adeno-associated virus (rAAV) encoding secondary lymphoid tissue chemokine (SLC) mature peptide gene. AAV Helper-Free system was used for rAAV-SLC package. The anti-tumor effect of SLC was detected by bearing tumor established from Hepal-6 cells both in C57BL/6J and nude mice. Flow cytometry analysis and IHC for Tumor-infiltrating T cells and CD11c+DCs were also investigated to explore the immunological mechanism. rAAV-SLC was successfully packaged in AAV293 cells and transfected Hepal-6 tumor cells at high efficiency. The anti-tumor effect was demonstrated by less tumor weight and longer survival outcome. Coincident with the anti-tumor response, local elaboration of SLC within the tumor bed elicited a heavy infiltration of CD4+, CD8+T cells and CD11c+ dendritic cells into the tumor sites. More importantly, there was higher infiltration of Foxp3+ regulatory T cells (Tregs). Local elaboration of SLC mediated by rAAV-SLC has strong T cell mediated anti-tumor effect. The study also suggested that Tregs in the tumor microenvironment tampered the anti-tumor effect. |
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