Intratumoral high Foxp3+ Tregs/CD8+ ratio was an independent predictor for the prognosis of gastric cancer. It can be inferred that a combination of deletion of Tregs and stimulation of CD8+ effector T cells may be an effective immunotherapy to prolong survival after surgery.
The chemokine receptor CCR7 is highly expressed in dendritic cells (DCs), T cells, and other immune effector cells. One of the high-affinity ligand that can bind to CCR7 is the secondary lymphoid tissue chemokine (SLC). The SLC/CCR7 axis plays an important role in the immune system by inducing the chemotaxis and migration of immune effector cells. In this study, we examined the effect of SLC at different concentrations (0, 50, 100, 200, 300, and 400 ng/mL) on the proliferation of bone-marrowderived dendritic cells (BMDCs). ELC (CCL19), another high-affinity ligand for CCR7, was used as the control at the same time. We found that SLC directly stimulated the proliferation of BMDCs and enhanced the antigen-presenting function and CCR7 expression. Western blot analysis showed that pNF-jBp65 was involved in this mechanism. We also found that the NF-jB inhibitor PDTC could specifically block the proliferation and CCR7 expression of BMDCs induced by SLC or ELC (200 ng/mL). The results suggested that there were cross-talk signals between the chemotaxis and proliferation of BMDCs involving the SLC/CCR7 axis. Anat Rec,
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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