title: T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer.
abstract: OBJECTIVE
  Studies have demonstrated that the generation of immunity to tumor antigens is associated with improved prognosis for many cancers. A candidate antigen is the folate receptor alpha (FRalpha), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRalpha immunity.
  
  
  METHODS
  Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRalpha, and tested for immunity in 30 breast (n = 17) or ovarian (n = 13) cancer patients and 18 healthy donors using enzyme-linked immunospot analysis.
  
  
  RESULTS
  Fourteen peptides were predicted, seven each from the carboxy- and amino-terminus halves of the protein. More than 70% of patients demonstrated immunity to at least one FRalpha peptide. Patients responded to an average of 3 +/- 0.5 peptides, whereas healthy donors responded to 1 +/- 0.4 peptides (P = .004). Five peptides were recognized by more than 25% of patients. Responses to three peptides were higher (P < .05) in patients than in healthy donors, suggesting augmented immunity. Compared with healthy individuals, patients developed higher immunity to the amino-terminus half of the receptor (P = .03). There was no difference between each group in the responses to nonspecific (P = .2) and viral stimuli (P = .5). Lastly, patients demonstrated elevated levels of FRalpha antibodies consistent with a coordinated immune response.
  
  
  CONCLUSIONS
  These findings demonstrate that the FRalpha is a target of the immune system in breast and ovarian cancer patients. Understanding which antigens are targeted by the immune system may be important for prognosis or immune-based therapies.
authors.affiliation: Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. knutson.keith@mayo.edu
authors.forename: Keith L
authors.initials: KL
authors.lastname: Knutson
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Krco
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Erskine
authors.forename: Karin
authors.initials: K
authors.lastname: Goodman
authors.forename: Linda E
authors.initials: LE
authors.lastname: Kelemen
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wettstein
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001943:Breast Neoplasms / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology*; D011237:Predictive Value of Tests; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D000939:Epitopes; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D007371:Interferon-gamma