Tumor-induced insufficiency in T cell activity and hyperproduction of interleukin-2 in rat giant hepatomas

The roles of lymphoid elements and apoptosis-related proteins in the develo pment of extremely large hepatomas were studied in rats. Hepatoma cells wer e inoculated subcutaneously into 6-week-old rats, and 4 months later the qu antities of T and B cells, macrophages, and cells positive for Fas, Fas lig and (FasL) and interleukin-2 (IL-2) were immunochemically evaluated in tumo rs. Grafting of hepatoma cells caused the development of giant tumors that could reach one-third of the rat's body weight. Within the hepatomas, almos t all CD8(+) T cells were destroyed as they passed from the tumoral stroma into the parenchyma and came in contact with tumor epithelial cells. This c ould be the consequence of IL-2 production, since about 90% of tumor cells were CD25(+). The tumoral mass increased despite the significant increase i n tumor necrosis. Cells with Ki67 or in mitosis, and cells positive for Fas and FasL were found only among tumor epithelial cells that were necrotic a nd never among viable cells. We suggest that progress in tumorigenesis is f acilitated by inhibition of T helper cells, and the extensive death of T ki ller cells is caused by the high levels of the tumor produced IL-2.