Robert Ian Seed

We are trying to elucidate the mechanism of AvB8 mediated TGF-B activation. We have shown that tumor cell expression of AvB8 results in enhanced tumor growth by promoting immune tolerance in the TME. Blocking avB8 from binding to and activating L-TGFB slows tumor growth in numerous syngeneic xenograft models. We are currently characterizing the immune cell phenotype in the TME of AvB8 expressing tumors with a focus on Treg differentiation. Adenocarcinomas are known to overexpress AvB8, but not cell surface associated L-TGFB. However, we know that immune cell subsets do express cell surface L-TGFB, but no AvB8. therefore we hypothesize that AvB8 expressed on tumor cells provides a platform for TGFB activation on infiltrating immune cells in the TME.