Downregulation of lymphocyte mitogenesis by breast cancer-associated p43

Placental isoferritin-associated p43 has proven to induce immune suppression during pregnancy in order to avoid rejection of the fetus' alloantigens by maternal lymphocytes. It has been demonstrated previously that p43 is also synthesized by breast cancer cells and can also be found on the surface of a subpopulation of T cells in women with this disease. Therefore, it was the aim of the present study to investigate if breast cancer-associated p43 has immunosuppressive properties. In 40 women undergoing surgical excision of a suspicious lump in their breast, blood was withdrawn and lymphocytes were isolated. Lymphocyte cultures were incubated with p43 antigen and anti-p43 antibody (CM-H-9). In a second series, lymphocyte mitogenesis was activated by addition of concanavalin A (Con A), Con A + p43 and Con A + anti-p43, respectively. While lymphocytes of breast cancer patients ( n = 21) and women with benign breast disease ( n = 19) incubated with p43 as well as with anti-p43 antibody did not show any difference in terms of incorporation of [ 3H]thymidine, activation of lymphocytes by addition of Con A was significantly inhibited after addition of p43 antigen in breast cancer patients compared to women with benign breast disease ( P = 0.0178). Analysis of prognostic factors for breast cancer showed that inhibition of lymphocyte mitogenesis was dependent on the degree of tumor differentiation and was significantly higher in well differentiated tumors (GI) compared with more dedifferentiated tumors (GIII). The present study shows that breast cancer-associated antigen p43 is able to induce immune suppression in breast cancer patients but not in women with benign breast disease.