APOPTOSIS IN RAT PROSTATIC ADENOCARCINOMA IS ASSOCIATED WITH RAPID INFILTRATION OF CYTOTOXIC T-CELLS AND ACTIVATED MACROPHAGES

Rats transplanted with the androgen-sensitive, syngeneic Dunning R3327 PAP prostatic tumor were castrated and treated with estrogen or vehic le for 4, 12 and 24 hr and for 6 weeks. Tumor growth was retarded by c astration and further inhibited by estrogen. Immediately after castrat ion, an increased number of activated macrophages and T-cells were fou nd in parallel with increasing apoptotic tumor cells. Administration o f an immunosuppressive drug, FK 506, abolished the growth-inhibitory e ffects of castration and estrogen. The tumor growth rate correlated ne gatively with the number of R73- and OX8-positive T-cells and NK cells and with the percentage of ED3-positive macrophages. There was a posi tive correlation between the percentage of TdT-mediated-dUTP nick end labeling (TUNEL)-positive apoptotic cells and that of ED3-positive cel ls. Our results suggest that apoptosis of prostatic carcinoma cells in duced by endocrine treatment in vivo is partly due to a rapid infiltra tion by immunocompetent cells. (C) 1997 Wiley-Liss, Inc.