title: Dendritic cells loaded with killed breast cancer cells induce differentiation of tumor-specific cytotoxic T lymphocytes.
abstract: BACKGROUND
  Early clinical trials, mostly in the setting of melanoma, have shown that dendritic cells (DCs) expressing tumor antigens induce some immune responses and some clinical responses. A major difficulty is the extension to other tumors, such as breast carcinoma, for which few defined tumor-associated antigens are available. We have demonstrated, using both prostate carcinoma and melanoma as model systems, that DCs loaded with killed allogeneic tumor cell lines can induce CD8+ T cells to differentiate into cytotoxic T lymphocytes (CTLs) specific for shared tumor antigens.
  
  
  METHODS
  The present study was designed to determine whether DCs would capture killed breast cancer cells and present their antigens to autologous CD4+ and CD8+ T cells.
  
  
  RESULTS
  We show that killed breast cancer cells are captured by immature DCs that, after induced maturation, can efficiently present MHC class I and class II peptides to CD8+ and CD4+ T lymphocytes. The elicited CTLs are able to kill the target cells without a need for pretreatment with interferon gamma. CTLs can be obtained by culturing the DCs loaded with killed breast cancer cells with unseparated peripheral blood lymphocytes, indicating that the DCs can overcome any potential inhibitory effects of breast cancer cells.
  
  
  CONCLUSIONS
  Loading DCs with killed breast cancer cells may be considered a novel approach to breast cancer immunotherapy and to identification of shared breast cancer antigens.
authors.affiliation: Centre Léon-Bérard, Laboratoire de thérapie cellulaire et greffes hématopoiètiques, Lyon, France. neidhard@lyon.fnclcc.fr
authors.forename: Eve-Marie
authors.initials: EM
authors.lastname: Neidhardt-Berard
authors.forename: Frederic
authors.initials: F
authors.lastname: Berard
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.forename: A Karolina
authors.initials: AK
authors.lastname: Palucka
mesh_terms: D017951:Antigen Presentation / Q000502:physiology; D000938:Antigen-Presenting Cells / Q000502:physiology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology*; D016923:Cell Death / Q000528:radiation effects; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000502:physiology; D005720:Gamma Rays; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020014:K562 Cells / Q000473:pathology; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma