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Modulation of the antitumor immune response by complement.

ABSTRACT: 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.

SUBMITTER: Markiewski MM

PROVIDER: S-EPMC2678913 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Modulation of the antitumor immune response by complement.

Markiewski Maciej M MM DeAngelis Robert A RA Benencia Fabian F Ricklin-Lichtsteiner Salome K SK Koutoulaki Anna A Gerard Craig C Coukos George G Lambris John D JD

Nature immunology 20080928 11

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 suppr ...[more]

PMID: 18820683

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