1. Complement-dependent modulation of antitumor immunity following radiation therapy.
- Author
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Elvington M, Scheiber M, Yang X, Lyons K, Jacqmin D, Wadsworth C, Marshall D, Vanek K, and Tomlinson S
- Subjects
- Animals, Apoptosis, Cell Line, Tumor, Complement Activation, Complement Inactivating Agents pharmacology, Complement Inactivating Agents therapeutic use, Dendritic Cells immunology, Lymphoma radiotherapy, Lymphoma therapy, Mice, Mice, Inbred C57BL, Neutrophil Infiltration, Recombinant Fusion Proteins pharmacology, Recombinant Fusion Proteins therapeutic use, Subcutaneous Tissue pathology, T-Lymphocytes immunology, Complement C3d antagonists & inhibitors, Immunomodulation, Lymphoma immunology
- Abstract
Complement is traditionally thought of as a proinflammatory effector mechanism of antitumor immunity. However, complement is also important for effective clearance of apoptotic cells, which can be an anti-inflammatory and tolerogenic process. We show that localized fractionated radiation therapy (RT) of subcutaneous murine lymphoma results in tumor cell apoptosis and local complement activation. Cotreatment of mice with tumor-targeted complement inhibition markedly improved therapeutic outcome of RT, an effect linked to early increases in apoptotic cell numbers and increased inflammation. Improved outcome was dependent on an early neutrophil influx and was characterized by increased numbers of mature dendritic cells and the subsequent modulation of T cell immunity. Appropriate complement inhibition may be a promising strategy to enhance a mainstay of treatment for cancer., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2014
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