Cellular and humoral immune responses to MUC1 mucin and tandem-repeat peptides in ovarian cancer patients and controls

The objective of this study was to demonstrate the presence of;proliferativ e T cell responses to human polymorphic epithelial mucin (MUC1) and its tan dem-repeat peptides in peripheral blood mononuclear cells (PBMC) from ovari an cancer patients and from controls and to correlate these cellular respon ses to a humoral response to MUC1. PBMC were obtained from 6 healthy women, from 13 women in the third trimester of pregnancy and from 21 ovarian canc er patients. Only 1 of the 6 healthy women showed a weak primary proliferat ive response (stimulation index, SI < 2) to a 20-mer MUC1 tandem-repeat pep tide in the presence of interleukin-2 (IL-2). In PBMC from 5/13 pregnant wo men (38%) a weak response could be induced by the 20-mer and/or 60-mer tand em-repeat peptides (SI less than or equal to 3.0) and in PBMC from 8/15 ova rian cancer patients (53%) 20-mer and/or 60-mer MUC1 tandem-repeat peptides induced primary responses (SI less than or equal to 5.4). MUC1 mucin purif ied from a breast tumor cell line and/or from urine of a healthy donor had a relatively strong stimulating effect (SI less than or equal to 19) on PBM C from 4 of 16 ovarian cancer patients (25%). In contrast, in PBMC of 9 ova rian cancer patients stimulated by the addition of a Candida albicans extra ct, MUC1 mucin strongly inhibited proliferation. This inhibition could part ially be abrogated by the addition of IL-2. MUC1 (CA 15.3 assay) and free c irculating MUC1 IgG and IgM antibodies (PEM.CIg assay) were determined in t he plasma of all subjects. The MUC1 and the free circulating MUC1 IgG antib ody plasma levels were significantly higher in the ovarian cancer patients than in the healthy women. Although no significant correlations were found between MUC1 mucin, MUC1 Ab plasma levels and the individual proliferative responses to the MUC1 antigens, an association may exist between them, sinc e all three are significantly higher in the ovarian cancer patients than in the healthy women.