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Complement in Cancer: Untangling an Intricate Relationship

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Journal Nat Rev Immunol
Date 2017 Sep 19
PMID 28920587
Citations 208
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Abstract

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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References
1.
Cho M, Rupaimoole R, Choi H, Noh K, Chen J, Hu Q . Complement Component 3 Is Regulated by TWIST1 and Mediates Epithelial-Mesenchymal Transition. J Immunol. 2016; 196(3):1412-8. PMC: 4724537. DOI: 10.4049/jimmunol.1501886. View

2.
Okroj M, Hsu Y, Ajona D, Pio R, Blom A . Non-small cell lung cancer cells produce a functional set of complement factor I and its soluble cofactors. Mol Immunol. 2007; 45(1):169-79. DOI: 10.1016/j.molimm.2007.04.025. View

3.
Wang Y, Sun S, Liu Q, Yu Y, Guo J, Wang K . Autocrine Complement Inhibits IL10-Dependent T-cell-Mediated Antitumor Immunity to Promote Tumor Progression. Cancer Discov. 2016; 6(9):1022-35. PMC: 5010476. DOI: 10.1158/2159-8290.CD-15-1412. View

4.
Ricklin D, Lambris J . Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013; 190(8):3831-8. PMC: 3623009. DOI: 10.4049/jimmunol.1203487. View

5.
Medof M, Gottlieb A, Kinoshita T, Hall S, Silber R, NUSSENZWEIG V . Relationship between decay accelerating factor deficiency, diminished acetylcholinesterase activity, and defective terminal complement pathway restriction in paroxysmal nocturnal hemoglobinuria erythrocytes. J Clin Invest. 1987; 80(1):165-74. PMC: 442215. DOI: 10.1172/JCI113043. View