Abstract
Abstract Promoting complement activation may enhance immunological mechanisms of anti-tumor antibodies for tumor destruction. However, complement activation components, such as C5a, trigger inflammation which can promote tumor growth. It has been demonstrated, in one tumor model, that C5a in the tumor can inhibit anti-tumor CD8 T cell responses through effects on myeloid-derived suppressor cells. We address the role of C5a on tumor growth by transfecting tumor cells with mouse C5a: SKOV-3 human ovarian carcinoma and RMA murine lymphoma. The two models allow us to study C5a in immunocompromised and immunocompetent hosts. In vitro growth kinetics of C5a, control vector (CV), or wild-type cells revealed no significant differences. In both models, tumor-bearing mice with C5a-transfected tumor cells have significantly less tumor burden as compared to CV tumors. In the immunocompromised model, DX5 CD11b NK cells and F4/80 macrophages infiltrated C5a expressing tumors with significantly greater frequency while VEGF and arginase production were significantly less. The syngeneic model revealed C5a leads to a greater tumor influx of CD11c and CD4 T cells. A greater percentage of CD4 T cells infiltrating RMA C5a tumors demonstrated an activated status, CD44hi CD62L low. Thus our studies demonstrate tumor C5a chemoattracts innate NK cells and macrophages while downregulating negative mediators, and promotes infiltration of important antigen-presenting cells and activated CD4 T effector cells.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call