Age-related changes of natural antitumor resistance in spontaneously hypertensive rats with T-cell depression.

We investigated the relationship between age-related changes in natural resistance and antitumor effects using a spontaneously hypertensive rat (SHR rat) strain which shows a progressive decline of the number of T-cells and their functions as a result of aging. The growth of a weakly antigenic mammary adenocarcinoma SST-2 was significantly suppressed in SHR rats ages 2 and 3 months, whereas in SHR rats ages 1 or 8 months no suppression of the tumor growth was observed. Splenic natural killer cell activity among the SHR rats was still low at 1 month, when the T-cell function is relatively intact; it reached a maximum level at 3 months and thereafter rapidly decreased. On the other hand, the cytostatic activity of peritoneal macrophages, which is also low at 1 month and becomes high at 3 months, thereafter remained at high levels until 8 months of age. That is, the kinetics of natural killer cell activity during the aging processes runs parallel to the function of suppressing tumor growth. Treatment with anti-asialomonoganglioside antiserum abrogated the suppressive activity of SST-2 tumor growth in 3-month-old SHR rats. Treatment with double stranded RNA polyinosinate-polycytidylate, an interferon inducer, produced significant suppression of the tumor growth in SHR rats ages 3 and 8 months. These results suggest that the participation of natural killer cells is a principal effector mechanism in the suppression of SST-2 tumor growth in SHR rats ages 2 and 3 months.