title: Chloroquine engages the immune system to eradicate irradiated breast tumors in mice.
abstract: OBJECTIVE
  This study used chloroquine to direct radiation-induced tumor cell death pathways to harness the antitumor activity of the immune system.
  
  
  METHODS
  Chloroquine given immediately after tumor irradiation increased the cure rate of MCaK breast cancer in C3H mice. Chloroquine blocked radiation-induced autophagy and drove MCaK cells into a more rapid apoptotic and more immunogenic form of cell death.
  
  
  RESULTS
  Chloroquine treatment made irradiated tumor vaccines superior at inducing strong interferon gamma-associated immune responses in vivo and protecting mice from further tumor challenge. In vitro, chloroquine slowed antigen uptake and degradation by dendritic cells, although T-cell stimulation was unaffected.
  
  
  CONCLUSIONS
  This study illustrates a novel approach to improve the efficacy of breast cancer radiation therapy by blocking endosomal pathways, which enhances radiation-induced cell death within the field and drives antitumor immunity to assist therapeutic cure. The study illuminates and merges seemingly disparate concepts regarding the importance of autophagy in cancer therapy.
authors.affiliation: Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California.
authors.forename: Josephine Anna
authors.initials: JA
authors.lastname: Ratikan
authors.forename: James William
authors.initials: JW
authors.lastname: Sayre
authors.forename: Dörthe
authors.initials: D
authors.lastname: Schaue
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001343:Autophagy / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000532:radiotherapy; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002738:Chloroquine / Q000494:pharmacology*; D003131:Combined Modality Therapy / Q000379:methods; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D011992:Endosomes / Q000187:drug effects / Q000276:immunology; D005260:Female; D016233:Immunotherapy, Active / Q000379:methods; D051379:Mice; D008809:Mice, Inbred C3H; D010047:Ovalbumin / Q000276:immunology / Q000493:pharmacokinetics*
chemical_list: C033666:fluorescein-thiocarbamyl-ovalbumin; D002738:Chloroquine; D010047:Ovalbumin