title: Complement-dependent modulation of antitumor immunity following radiation therapy.
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.
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Michelle
authors: M
authors: Elvington
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Melissa
authors: M
authors: Scheiber
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Xiaofeng
authors: X
authors: Yang
authors: Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Katherine
authors: K
authors: Lyons
authors: Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Dustin
authors: D
authors: Jacqmin
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Casey
authors: C
authors: Wadsworth
authors: Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: David
authors: D
authors: Marshall
authors: Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Kenneth
authors: K
authors: Vanek
authors: Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, USA. Electronic address: tomlinss@musc.edu.
authors: Stephen
authors: S
authors: Tomlinson
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003167:Complement Activation; D015933:Complement C3d / Q000037:antagonists & inhibitors*; D051056:Complement Inactivating Agents / Q000494:pharmacology / Q000627:therapeutic use; D003713:Dendritic Cells / Q000276:immunology; D056747:Immunomodulation; D008223:Lymphoma / Q000276:immunology* / Q000532:radiotherapy / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D040521:Subcutaneous Tissue / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C527099:CR2-Crry fusion protein, mouse; D051056:Complement Inactivating Agents; D011993:Recombinant Fusion Proteins; D015933:Complement C3d