ACTIVATED LYMPHOCYTES FROM BREAST-CANCER PATIENTS EXPRESS THE CHARACTERISTICS OF TYPE-2 HELPER-CELLS - A POSSIBLE ROLE FOR BREAST-CANCER-ASSOCIATED P43

P43, a breast cancer-associated antigen, has been repeatedly described as an immunosuppressive factor. The objective of the present study wa s to investigate whether immune dysregulation induced by p43 affects t he profile of cytokines secreted by mitogen-stimulated lymphocytes in breast cancer patients as compared with stimulated lymphocytes in wome n with benign tumors. The study consisted of 32 women undergoing surgi cal excision for a suspicious lesion in their breast. Histology reveal ed malignant breast disease in 20 patients and benign lesions in 10 pa tients. Lymphocytes isolated from peripheral blood were activated by C onconavalin A (Con A) with and without the addition of p43 and the con centrations of cytokines (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10 and IL-6) secreted into the culture medium were determined. Lymphocytes of patients with malignant breast disease stimulated with Con A secreted a significantly higher concentration of IL-10 compared with lymphocyt es of patients with benign tumors. No significant differences were fou nd between the two groups regarding the levels of IL-2, TNF-alpha, IFN -gamma and IL-4. Cytokine concentrations were analyzed according to th e type 1/type 2 cytokine profile (IL-2, TNF and IFN-gamma and IL-4, IL -6 and IL-10, respectively). This analysis revealed no significant dif ferences in IL-2, TNF or IFN-gamma between benign and malignant tumors . However, in the type 2 cytokines, lymphocytes from cancer patients s ecreted significantly higher levels of IL-4 (27.3 +/- 7.2 U/ml) and IL -10 (44.1 +/- 22.3 U/ml) than did the lymphocytes from patients with b enign disease (21.4 +/- 7.3 and 1.8 +/- 0.3 U/ml, respectively). The a ddition of p43 to the culture medium significantly enhanced the levels of IL-4 secreted by lymphocytes in both groups of patients (malignant disease, from 27.3 +/- 9.2 to 40.7 +/- 6.3 U/ml; benign disease, from 21.4 +/- 7.3 to 28.4 +/- 2.1 U/ml). P43 antigen significantly enhance d the low levels of IL-10 in the benign lymphocytes (from 1.8 +/- 0.4 to 8.4 +/- 1.5 U/ml) while the high levels of IL-10 secreted by the PB L in patients with malignant tumors were not significantly increased ( 44.1 +/- 22.3 versus 50.1 +/- 12.6 U/ml). The study showed a differenc e in the immune response of lymphocytes between malignant and benign t umors. When the current results were analyzed according to the type of response, i.e. in terms of whether at least two cytokines of either t ype 1 or type 2 were elevated, a significant type 2 response was obser ved in the PBL of patients with malignant breast cancer (IL-10 and IL- 4). These results may explain why antitumor response is impaired in pa tients with breast cancer. (C) 1998 Elsevier Science Ireland Ltd.