title: Natural immunosurveillance against spontaneous, autochthonous breast cancers revealed and enhanced by blockade of IL-13-mediated negative regulation.
abstract: BACKGROUND
  We and others previously observed immunosurveillance against transplantable tumors in mice, and enhancement thereof by blockade of negative regulation by T reg cells or the NKT-IL-13-myeloid cell-TGF-beta regulatory circuit. However, it was unknown whether natural immunosurveillance inhibits growth of completely spontaneous autochthonous tumors, and whether it can be improved by inhibition of negative regulation.
  
  
  METHODS
  To examine the existence of T cell-mediated immunosurveillance against spontaneous tumors, BALB-neuT mice were treated with anti-CD4 and/or anti-CD8. A role for IL-13 in the suppression of immunosurveillance was investigated by treating mice with IL-13 inhibitor.
  
  
  RESULTS
  We show that even spontaneous autochthonous breast carcinomas arising in Her-2/neu transgenic mice appear more quickly when the mice are depleted of T cells, evidence for T-cell mediated immunosurveillance slowing tumor growth. This immunosurveillance could be further enhanced by blockade of IL-13 (but not IL-4) which slowed the appearance of these autologous tumors compared to control antibody-treated mice.
  
  
  CONCLUSIONS
  Thus, even completely spontaneous, autochthonous breast cancers can be controlled in part by natural immunosurveillance, and blockade of negative regulation can improve this control.
authors.affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Building 10-Room 6B-12, 9000 Rockville Pk, Bethesda, MD 20892-1578, USA .
authors.forename: Jong Myun
authors.initials: JM
authors.lastname: Park
authors.forename: Masaki
authors.initials: M
authors.lastname: Terabe
authors.forename: Debra D
authors.initials: DD
authors.lastname: Donaldson
authors.forename: Guido
authors.initials: G
authors.lastname: Forni
authors.forename: Jay A
authors.initials: JA
authors.lastname: Berzofsky
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018793:Interleukin-13 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015166:Monitoring, Immunologic / Q000379:methods*; D009368:Neoplasm Transplantation; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D016212:Transforming Growth Factor beta; D015847:Interleukin-4