title: TGF-alpha as a candidate tumor antigen for renal cell carcinomas.
abstract: OBJECTIVE
  Patients with renal cell carcinomas (RCC) have few treatment options, underscoring the importance of developing new approaches such as immunotherapy. However, few tumor associated antigens (TAA), which can be targeted by immunotherapy, have been identified for this type of cancer. von Hippel-Lindau clear cell RCC (VHL(-/-)RCC) are characterized by mutations in the VHL tumor suppressor gene. Loss of VHL function causes the overexpression of transforming growth factor (TGF)-alpha, leading us to hypothesize that TGF-alpha could be a potential TAA for immunotherapy of kidney cancer, which was evaluated in this study.
  
  
  RESULTS
  We first confirmed the absent or weak expression of TGF-alpha in important normal tissues as well as its overexpression in 61% of renal tumors in comparison to autologous normal kidney tissues. In addition, we demonstrated the immunogenicity of TGF-alpha, by expanding many T cell lines specific for certain TGF-alpha peptides or the mature TGF-alpha protein, when presented by major histocompatibility complex (MHC) molecules on the surface of antigen-presenting cells. Interestingly, some of these TGF-alpha-specific T cells were polyfunctionals and secreted IFN-gamma, TNF-alpha and IL-2.
  
  
  CONCLUSIONS
  We have shown that TGF-alpha is a valid candidate TAA, which should allow the development of a targeted immunotherapy.
authors.affiliation: Department of Medicine, CRCHUM-Hôpital Notre-Dame, Université de Montréal, Montreal, Canada.
authors.forename: Sandy
authors.initials: S
authors.lastname: Pelletier
authors.forename: Simon
authors.initials: S
authors.lastname: Tanguay
authors.forename: Stephen
authors.initials: S
authors.lastname: Lee
authors.forename: Lakshman
authors.initials: L
authors.lastname: Gunaratnam
authors.forename: Nathalie
authors.initials: N
authors.lastname: Arbour
authors.forename: Réjean
authors.initials: R
authors.lastname: Lapointe
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D045744:Cell Line, Tumor; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000276:immunology*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D010455:Peptides; D016211:Transforming Growth Factor alpha; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human