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Age-related changes of natural antitumor resistance in spontaneously hypertensive rats with T-cell depression
Abstract:
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.
Insights
Aging spontaneously hypertensive rats (SHR rats) show age-dependent changes in natural killer cell activity, correlating with suppressed tumor growth. Natural killer cells are key to this age-related antitumor effect.
Area of Science:
- Immunology
- Aging Research
- Cancer Biology
Background:
- Spontaneously hypertensive rats (SHR rats) exhibit age-related declines in T-cell number and function.
- Understanding age-related immune system changes is crucial for cancer research.
Purpose of the Study:
- To investigate the link between aging, immune function, and antitumor effects in SHR rats.
- To identify the immune mechanisms responsible for suppressing tumor growth in aging rats.
Main Methods:
- Utilized SHR rats of various ages (1, 2, 3, and 8 months) to study tumor growth.
- Assessed splenic natural killer (NK) cell activity and peritoneal macrophage cytostatic activity.
- Administered anti-asialomonoganglioside antiserum and polyinosinate-polycytidylate (a double-stranded RNA interferon inducer).
Main Results:
- Tumor growth of SST-2 mammary adenocarcinoma was suppressed in 2- and 3-month-old SHR rats, but not in 1- or 8-month-old rats.
- NK cell activity peaked at 3 months and declined thereafter, paralleling tumor suppression.
- Macrophage activity increased by 3 months and remained high, while NK cell activity correlated directly with tumor suppression.
Conclusions:
- Natural killer cell activity kinetics align with the age-dependent suppression of SST-2 tumor growth in SHR rats.
- NK cells appear to be the primary effector mechanism for suppressing tumor growth in younger SHR rats.
- Interferon induction showed potential for tumor suppression in older SHR rats.