Effects of cyclophosphamide and soluble tumor-associated antigens on lymphoid infiltration, proliferative activity and rate of apoptosis in chemically-induced rat mammary tumors

The aim of this study was to analyze the roles of proliferative activity, lymphoid infiltration and apoptotic rate in the cellular mechanism underlying the promotion effects of soluble tumor-associated antigens (sTAA) in mammary cancer in rats treated with the anticancer drug cyclophosphamide (CPA). Studies were performed on the following groups of rats: i) control tumor-bearing rats, ii) tumor-bearing rats treated with sTAA, iii) tumor-bearing rats treated with CPA, iv) tumor-bearing rats treated with CPA and sTAA. Mammary gland cancer was induced with dimethylbenz(a)anthracene (DMBA), and the rate of lymphoid infiltration, T cell content (CD4+ and CD8+ cells), and mitotic and apoptotic indices in tumors were evaluated. In control tumor-bearing rats, high lymphoid proliferation, as well as a high number of CD8+ cells, was found in tumors. Treatment with sTAA further significantly increased the total number of lymphoid cells and the number of CD8+ lymphocytes. CPA sharply decreased the production of all lymphoid cells studied, especially of CD4+ lymphocytes. The combined treatment of CPA and sTAA increased the number of lymphoid cells, although they did not reach control levels. The mitotic index significantly decreased as a result of the treatment with CPA alone and especially after the combined treatment with CPA and sTAA. The results of our experiments demonstrate that vaccination with sTAA actively promotes the generation of the host's antitumor immune response. This is manifested in inhibited proliferative activity of tumor cells, stimulated production of T lymphocytes and increased rate of apoptosis among tumor cells.