Tumor-preventive effects of the soluble p53 antigen on chemically-induced skin cancer in mice

Background. The tumor-suppressive effects of the rat soluble p53 antigen on chemically induced skin cancer in mice and the role of the spleen in the immune response to a carcinogen and vaccination were studied. Methods: Skin cancer was induced by 9,10-dimethyl-1,2-benzanthracene (DMBA). Vaccination was initiated by injection of liposomes with the soluble p53 antigen (10-12 μg/mouse) while boosters were with the p53 mixed with Freund's incomplete adjuvant (two injections). Four months later, the spleen and tumors were removed and examined morphometrically (determination of areas of different spleen's zones) and immunohistochemically (determination of number of B lymphocytes and macrophages, apoptotic index). The following groups of mice were studied: A) control non treated mice; Bl) tumor-free mice treated with a carcinogen; B2) tumor-bearing mice; Cl) tumor free vaccinated mice exposed to a carcinogen; C2) tumor-bearing vaccinated mice. Results: Mice exposed to a carcinogen which were tumor-free, displayed high proliferative activity of the spleenic lymphoid constitutes such as B lymphocytes and macrophages. This was reflected in the remarkable transformation of B lymphocytes in lymphoblasts (blast transformation) and an increase in the area of germinal centers, compared to untreated controls. In tumor-bearing non vaccinated mice, significantly more spleenic apoptotic cells were found than in their tumor-free counterparts. Shrinkage of the mantle layer and a decrease in cellular density of follicles were seen in all carcinogen-treated mice, reflecting the reduced total production of lymphoid cells, and thus the insufficiency of the immune reaction of animals to a carcinogen. A sharp decrease in the apoptotic index in the spleen of tumor-free mice may reflect an inhibition of apoptotic activity of the spleen by a carcinogen. Vaccination with the soluble p53 protein decreased the incidence of tumors and their size, significantly increased the apoptotic index within tumors, and reversed the splenic parameters of immune insufficiency. Conclusions: The immune system is active during tumorigenesis. Vaccination with the soluble p53 antigen had positive tumor-suppressive effects. The findings may facilitate the development of vaccines for the prevention of recurrent cancers in humans.