Article: article from journal or magazin.
Modulation of the antitumor immune response by complement.
Publication types: Journal Article ; Research Support, N.I.H., ExtramuralPublication Status: ppublish
The involvement of complement-activation products in promoting tumor growth has not yet been recognized. Here we show that the generation of complement C5a in a tumor microenvironment enhanced tumor growth by suppressing the antitumor CD8(+) T cell-mediated response. This suppression was associated with the recruitment of myeloid-derived suppressor cells into tumors and augmentation of their T cell-directed suppressive abilities. Amplification of the suppressive capacity of myeloid-derived suppressor cells by C5a occurred through regulation of the production of reactive oxygen and nitrogen species. Pharmacological blockade of the C5a receptor considerably impaired tumor growth to a degree similar to the effect produced by the anticancer drug paclitaxel. Thus, our study demonstrates a therapeutic function for complement inhibition in the treatment of cancer.
Animals, Complement Activation, Complement C3-C5 Convertases/genetics, Complement C5a/antagonists & inhibitors, Complement C5a/immunology, Down-Regulation, Female, Immunosuppression, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Mutant Strains, Myeloid Cells/immunology, Myeloid Cells/metabolism, Neoplasms/immunology, Neoplasms/therapy, Reactive Nitrogen Species/metabolism, Reactive Oxygen Species/metabolism, Receptor, Anaphylatoxin C5a/antagonists & inhibitors, Receptor, Anaphylatoxin C5a/immunology, Signal Transduction, T-Lymphocytes, Cytotoxic/immunology, Xenograft Model Antitumor Assays
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