Sex-related differences in tumor progression associated with altered lymphocyte circulation.

Male and female ACI rats were inoculated with the syngeneic H-4-II-E hepatoma, and the natural history of the tumor, histopathology, and lymphocyte migration were studied. The tumor formed a.s.c. mass in all 16 males and in 22 of the 26 females given injections. In the males, tumors progressed, and all animals died with the mean survival time of 54 days. Complete tumor regression was observed in all but two females. In the females, there was prominent lymphocytic infiltration of the tumor, while males had no cellular reaction at the tumor site. The regional lymph nodes in males usually contained metastases and were nonreactive. The female lymph nodes did not contain metastases but contained many lymphocytes within the peripheral sinus and sinusoids. Six male-female pairs were castrated before tumor inoculation. Castration had no effect on the natural history or the etiology of the tumor. Comparing seven normal control male-female littermate pairs, there were no differences in lymphocyte accumulation in the lymph nodes 22 hr following injection of 51Cr-labeled syngeneic lymphocytes. In seven tumor-bearing male-female littermate pairs, there was a significant decrease in lymphocyte migration to the lymph nodes (p less than 0.001) in tumor-bearing males as compared to that in both their female littermates and control males. Depressed lymphocyte circulation in the males was associated with rapid progression of tumors resulting in the death of the animals. Unimpaired lymphocyte mobilization in the tumor-bearing females was associated with complete regression in most animals.