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Nature Immunology 9, 1225–1235 (1 November 2008) | doi:10.1038/ni.1655

Modulation of the antitumor immune response by complement

Maciej M Markiewski , Robert A DeAngelis , Fabian Benencia , Salome K Ricklin-Lichtsteiner , Anna Koutoulaki , Craig Gerard , George Coukos & John D Lambris

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.