Effects of the soluble low-molecular-mass proteins on spleen activity and cellular composition of infiltrates in rat mammary gland tumors

We showed previously that soluble low-molecular-mass tumor-associated antig ens (TAA) could suppress chemically-induced tumorigenesis. In this study, w e analyzed the mechanism of those findings. Studies were performed on the s pleen and mammary grand tumors obtained from the following groups of rats: i) control rats treated with dimethylbenz(alpha )antracene (DMBA), ii) vacc inated and carcinoentreated rats with non regressed tumors, iii) vaccinated and carcinogen-treated rats with regressed tumors. Different zones of the spleen and tumors and their cellular content (Ki67(+) and CD8(+) cells, and macrophages) were analyzed morphometrically and immunohistochemically. Rea ction of the spleen to vaccination was manifested in a significant increase in all areas of the white pulp and in a decrease in the size of the red pu lp. The total number of cells in the white pulp (germinal center and PALS) and in the marginal zone was significantly higher in the spleen of rats wit h regressed tumors. The number of Ki67(+) cells decreased significantly in both groups of vaccinated rats, but most prominently in the marginal zone a nd the red pulp in rats with regressed tumors. An increased number of CD8() lymphocytes and macrophages was also seen in the red pulp. Different area s of the tumors (peripheral vs, inside at depth) showed different responses to vaccination and this difference was related to conditions of carcinogen esis, i.e. non-regressed vs, regressed tumors. In regressed tumors, all par ameters studied were easily distinguishable in both areas of the tumors, wh ile in non-regressed tumors, a marked distinction was seen only at their pe riphery. In regressed tumors, a negative correlation was seen at depth tumo rs between the number of Ki67(+) cells and the number of CD8(+) lymphocytes (r=-0.48). The findings indicated a strict antitumor effect of vaccination with the soluble low-molecular-mass TAA, which prevents the development of insufficiency of the immune system when an intensive immune reaction takes place.