T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer

Keith L. Knutson, Christopher J. Krco, Courtney L. Erskine, Karin Goodman, Linda E. Kelemen, Peter J. Wettstein, Philip S. Low, Lynn C. Hartmann, Kimberly R. Kalli

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58 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4254-4261
Number of pages8
JournalJournal of Clinical Oncology
Volume24
Issue number26
DOIs
StatePublished - Sep 10 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Knutson, K. L., Krco, C. J., Erskine, C. L., Goodman, K., Kelemen, L. E., Wettstein, P. J., Low, P. S., Hartmann, L. C., & Kalli, K. R. (2006). T-cell immunity to the folate receptor alpha is prevalent in women with breast or ovarian cancer. Journal of Clinical Oncology, 24(26), 4254-4261. https://doi.org/10.1200/JCO.2006.05.9311