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Nat Rev Immunol. 2018 Jan;18(1):5-18. doi: 10.1038/nri.2017.97. Epub 2017 Sep 18.

Complement in cancer: untangling an intricate relationship.

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Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania 19104, Philadelphia, Pennsylvania, USA.
National Center for Scientific Research 'Demokritos', Athens 15310, Greece.
Department of Pharmaceutical Sciences, University of Basel, Basel 4056, Switzerland.
Humanitas Clinical and Research Center and Humanitas University, Rozzano-Milan 20089, Italy.


In tumour immunology, complement has traditionally been considered as an adjunctive component that enhances the cytolytic effects of antibody-based immunotherapies, such as rituximab. Remarkably, research in the past decade has uncovered novel molecular mechanisms linking imbalanced complement activation in the tumour microenvironment with inflammation and suppression of antitumour immune responses. These findings have prompted new interest in manipulating the complement system for cancer therapy. This Review summarizes our current understanding of complement-mediated effector functions in the tumour microenvironment, focusing on how complement activation can act as a negative or positive regulator of tumorigenesis. It also offers insight into clinical aspects, including the feasibility of using complement biomarkers for cancer diagnosis and the use of complement inhibitors during cancer treatment.

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