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Kochanek DM, Ghouse SM, Karbowniczek MM, et al. Complementing Cancer Metastasis. Front Immunol. 2018;9:1629doi: 10.3389/fimmu.2018.01629.
Kochanek, D. M., Ghouse, S. M., Karbowniczek, M. M., & Markiewski, M. M. (2018). Complementing Cancer Metastasis. Frontiers in immunology, 91629. https://doi.org/10.3389/fimmu.2018.01629
Kochanek, Dawn M, et al. "Complementing Cancer Metastasis." Frontiers in immunology vol. 9 (2018): 1629. doi: https://doi.org/10.3389/fimmu.2018.01629
Kochanek DM, Ghouse SM, Karbowniczek MM, Markiewski MM. Complementing Cancer Metastasis. Front Immunol. 2018 Jul 16;9:1629. doi: 10.3389/fimmu.2018.01629. eCollection 2018. PMID: 30061895; PMCID: PMC6054933.
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Front Immunol. 2018 Jul 16;9:1629. doi: 10.3389/fimmu.2018.01629. eCollection 2018.

Complementing Cancer Metastasis.

Frontiers in immunology

Dawn M Kochanek, Shanawaz M Ghouse, Magdalena M Karbowniczek, Maciej M Markiewski

Affiliations

  1. Department of Immunotherapeutics and Biotechnology, School of Pharmacy, Texas Tech University Health Sciences Center, Abilene, TX, United States.

PMID: 30061895 PMCID: PMC6054933 DOI: 10.3389/fimmu.2018.01629

Abstract

Complement is an effector of innate immunity and a bridge connecting innate immunity and subsequent adaptive immune responses. It is essential for protection against infections and for orchestrating inflammatory responses. Recent studies have also demonstrated contribution of the complement system to several homeostatic processes that are traditionally not considered to be involved in immunity. Thus, complement regulates homeostasis and immunity. However, dysregulation of this system contributes to several pathologies including inflammatory and autoimmune diseases. Unexpectedly, studies of the last decade have also revealed that complement promotes cancer progression. Since the initial discovery of tumor promoting role of complement, numerous preclinical and clinical studies demonstrated contribution of several complement components to regulation of tumor growth through their direct interactions with the corresponding receptors on tumor cells or through suppression of antitumor immunity. Most of this work, however, focused on a role of complement in regulating growth of primary tumors. Only recently, a few studies showed that complement promotes cancer metastasis through its contribution to epithelial-to-mesenchymal transition and the premetastatic niche. This latter work has shown that complement activation and generation of complement effectors including C5a occur in organs that are target for metastasis prior to arrival of the very first tumor cells. C5a through its interactions with C5a receptor 1 inhibits antitumor immunity by activating and recruiting immunosuppressive cells from the bone marrow to the premetastatic niche and by regulating function and self-renewal of pulmonary tissue-resident alveolar macrophages. These new advancements provide additional evidence for multifaceted functions of complement in cancer.

Keywords: alveolar macrophages; cancer; complement system proteins; epithelial–mesenchymal transition; metastasis; myeloid-derived suppressor cells

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