Article abstract
Nature Immunology 9, 1225 - 1235 (2008)
Published online: 28 September 2008 | doi:10.1038/ni.1655
Modulation of the antitumor immune response by complement
Maciej M Markiewski1, Robert A DeAngelis1, Fabian Benencia2,4, Salome K Ricklin-Lichtsteiner1, Anna Koutoulaki1, Craig Gerard3, George Coukos2 & John D Lambris1
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.
- Department of Pathology and Laboratory Medicine, Medical School of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
- Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
- Pulmonary Division, Children's Hospital, Boston, Massachusetts 02215, USA.
- Present address: Department of Biomedical Sciences, College of Osteopathic Medicine and Biomedical Engineering Program, Russ College of Engineering and Technology, University of Ohio, Athens, Ohio 45701, USA.
Correspondence to: John D Lambris1 e-mail: lambris@upenn.edu
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