Modulation of the anti-tumor immune response by complement

By M. Markiewski, R. DeAngelis, F. Benencia, Salome K. Ricklin-Lichtsteiner, A. Koutoulaki, C. Gerard, George Coukos, John D Lambris. Nature Immunology, 2008

761 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/7fdd86b04550a3bc98905057f6f547806476bf4c

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Citations in the corpus

Complement - a key system for immune surveillance and homeostasis (2010, background): “Unexpectedly, the dogma that complement protects against tumors was further challenged when a recent study showed that classical pathway-induced generation of C5a in the tumor microenvironment leads to significant progression in tumor growth in a mouse model of cervical cance”
The Role of the Anaphylatoxins in Health and Disease (2009, positive): “Importantly, in a model of cervical cancer, genetic or pharmacological C5aR targeting resulted in decreased numbers ofMDSCswithin the tumor, associatedwithhighnumbers of CD8+ effector T cells and decreased tumor growth (Markiewski et al., 2008).”
Myeloid-Derived Suppressor Cells: Linking Inflammation and Cancer (2009, background): “Both of these activities resulted in more potent MDSC that were more suppressive for T cells (99).”
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A Low-Abundance Biofilm Species Orchestrates Inflammatory Periodontal Disease through the Commensal Microbiota and the Complement Pathway (2011, methodology): “…Cell Host & Microbe 10, 497–506, November 17, 2011 ª2011 Els Cha-A(D)R] (acetylated phenylalanine—[ornithine-proline-(D)cyclohexylalanine-alanine-(D)arginine]), were synthesized in the laboratory of one of the coauthors (J.D.L.) as previously described (Finch et al., 1999; Markiewski et al., 2008).”
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Complement System Part II: Role in Immunity (2015, background): “C5a is known to be a powerful chemoattractant molecule and plays a critical role in the inflammatory response by recruiting immune cells such as macrophages (100), neutrophils (101), basophils (102), and myeloid-derived suppressor cells (MDSCs) (103).”
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm (2010, background): “In a different setting, complement components have been linked to the recruitment of cancer-promoting myelomonocytic cells in transplante”
Complement System Part I – Molecular Mechanisms of Activation and Regulation (2015, background): “C5a also recruits T-cells (260) and myeloid-derived suppressor cells (261) that constitutively express C5aR.”