The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector.
Bottom Line: 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.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.
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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Mentions: Because SLC is chemotactic for T cells and DCs, we hypothesized that SLC expressed from tumor cells would elicit migration of these cells to the tumor site. To quantify the number of infiltrating CD4+ and CD8+T cell lymphocytes as well as CD11c+DCs were determined by flow cytometry and IHC analysis. These analysis illustrated that SLC-expression induced significantly higher numbers of CD4+, CD8+T cells and CD11c+DCs recruitment when compared to control (p < 0.01, as shown in Fig. 3). A modest increase in infiltrated immune cells was also observed in rAAV-GFP pre-infected tumors.Fig. 3