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The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector.

Li R, Hu H, Ma H, Chen L, Zhou B, Liu Y, Liang C - Mol. Biol. Rep. (2013)

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.

View Article: PubMed Central - PubMed

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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Related in: MedlinePlus

The observed antitumor effect of rAAV-SLC was immune-mediated. a The collected cells from tumor samples were stained FITC-CD11c, FITC-CD3 together with PE-CD4 or PE-CD8 for flow cytometric evaluation. Compared to control and rAAV-GFP, significantly higher numbers of CD11c+dendritic cells, CD4+T cells and CD8+T cells infiltration in SLC-treated mice were observed. Bars SD, *p < 0.05, **p < 0.01; i.t., intra-tumor injection; b serial 5 μm-thick Cryostat sections of tumor samples were performed by incubation with mAbs recognizing CD11c+dendritic cells, CD4+T cells and CD8+T cells. Positive cells were detected by DAB staining
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Fig3: The observed antitumor effect of rAAV-SLC was immune-mediated. a The collected cells from tumor samples were stained FITC-CD11c, FITC-CD3 together with PE-CD4 or PE-CD8 for flow cytometric evaluation. Compared to control and rAAV-GFP, significantly higher numbers of CD11c+dendritic cells, CD4+T cells and CD8+T cells infiltration in SLC-treated mice were observed. Bars SD, *p < 0.05, **p < 0.01; i.t., intra-tumor injection; b serial 5 μm-thick Cryostat sections of tumor samples were performed by incubation with mAbs recognizing CD11c+dendritic cells, CD4+T cells and CD8+T cells. Positive cells were detected by DAB staining

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


The anti-tumor effect and increased tregs infiltration mediated by rAAV-SLC vector.

Li R, Hu H, Ma H, Chen L, Zhou B, Liu Y, Liang C - Mol. Biol. Rep. (2013)

The observed antitumor effect of rAAV-SLC was immune-mediated. a The collected cells from tumor samples were stained FITC-CD11c, FITC-CD3 together with PE-CD4 or PE-CD8 for flow cytometric evaluation. Compared to control and rAAV-GFP, significantly higher numbers of CD11c+dendritic cells, CD4+T cells and CD8+T cells infiltration in SLC-treated mice were observed. Bars SD, *p < 0.05, **p < 0.01; i.t., intra-tumor injection; b serial 5 μm-thick Cryostat sections of tumor samples were performed by incubation with mAbs recognizing CD11c+dendritic cells, CD4+T cells and CD8+T cells. Positive cells were detected by DAB staining
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824217&req=5

Fig3: The observed antitumor effect of rAAV-SLC was immune-mediated. a The collected cells from tumor samples were stained FITC-CD11c, FITC-CD3 together with PE-CD4 or PE-CD8 for flow cytometric evaluation. Compared to control and rAAV-GFP, significantly higher numbers of CD11c+dendritic cells, CD4+T cells and CD8+T cells infiltration in SLC-treated mice were observed. Bars SD, *p < 0.05, **p < 0.01; i.t., intra-tumor injection; b serial 5 μm-thick Cryostat sections of tumor samples were performed by incubation with mAbs recognizing CD11c+dendritic cells, CD4+T cells and CD8+T cells. Positive cells were detected by DAB staining
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

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.

View Article: PubMed Central - PubMed

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.

Show MeSH
Related in: MedlinePlus