T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer.
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.
Knutson
Keith L
KL
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. knutson.keith@mayo.edu
Krco
Christopher J
CJ
Erskine
Courtney L
CL
Goodman
Karin
K
Kelemen
Linda E
LE
Wettstein
Peter J
PJ
Low
Philip S
PS
Hartmann
Lynn C
LC
Kalli
Kimberly R
KR
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*
D002352:Carrier Proteins; D000939:Epitopes; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D007371:Interferon-gamma