TY - JOUR
T1 - T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer
AU - Knutson, Keith L.
AU - Krco, Christopher J.
AU - Erskine, Courtney L.
AU - Goodman, Karin
AU - Kelemen, Linda E.
AU - Wettstein, Peter J.
AU - Low, Philip S.
AU - Hartmann, Lynn C.
AU - Kalli, Kimberly R.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2006/9/10
Y1 - 2006/9/10
N2 - Purpose: 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 (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity. Methods: Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, 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 FRα 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 FRα antibodies consistent with a coordinated immune response. Conclusion: These findings demonstrate that the FRα 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.
AB - Purpose: 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 (FRα), which is overexpressed in breast and ovarian cancers. Our goal in this study was to attain a better understanding of the extent of endogenous FRα immunity. Methods: Using a CD4+ T cell epitope prediction algorithm, we predicted promiscuous epitopes of FRα, 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 FRα 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 FRα antibodies consistent with a coordinated immune response. Conclusion: These findings demonstrate that the FRα 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.
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U2 - 10.1200/JCO.2006.05.9311
DO - 10.1200/JCO.2006.05.9311
M3 - Article
C2 - 16908932
AN - SCOPUS:33749016477
SN - 0732-183X
VL - 24
SP - 4254
EP - 4261
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 26
ER -