T cell-dependent antibody responses against aberrantly expressed cyclin B1 protein in patients with cancer and premalignant disease.

Abstract

Cyclin B1-derived peptides were shown by us to be targets of tumor-specific CD8(+) T cells in patients with breast and head and neck cancer. We obtained further evidence of cyclin B1 immunogenicity and its potential to serve as a tumor-specific antigen by analyzing its ability to elicit T cell-dependent humoral immune responses in vivo in patients with different types of tumors. Recombinant cyclin B1 protein from two different sources was purified and used as antigen in ELISA assays to test sera from patients with breast, pancreatic, colon, and lung cancer for the presence of anti-cyclin B1 antibody. We also analyzed patients with benign lung disease, premalignant disease, and a known history of heavy smoking. Cyclin B1 elicits helper T cell-dependent antibody responses in vivo. Tumors with higher level of cyclin B1 expression elicit higher anti-cyclin B1 antibody levels. Antibodies in patients with breast and colon cancer are primarily of the IgG isotype whereas patients with pancreatic and lung cancer have in addition anti-cyclin B1 IgA. Cyclin B1-specific IgG was also detected in long-term smokers and in patients with preneoplastic lung disease. Immune responses to aberrantly expressed cyclin B1 in tumors and premalignant lesions should be further explored as diagnostic and prognostic markers, in addition to their immunotherapeutic potential.