Antitumor Effect of Recombinant Human Interleukin‐2 on the Growth of Murine Hemangioendothelioma D14 in Nude Mice: Occurrence of Large Granular Cells in the Tumor

The antitumor effect of recombinant human interleukin‐2 (rIL‐2) on murine hemangioendothelioma D14 (D14) in female BALB/c‐nu/nu mice was examined histologically. D14 cells which had been maintained in vitro were transplanted subcutaneously into nude mice on day 0 (1 × 10(7) cells/mouse). The mice with established tumor on day 28 received rIL‐2 subcutaneously at a dose of 20 μg/mouse/ day for 35 days. On day 63, the mice were killed, and the tumor, spleen and bone marrow were examined histologically. In the mice that had received rIL‐2, tumor growth was significantly suppressed. Histologically, there was marked infiltration of large granular cells (about 15‐30 μ in diameter) in the tumors. In the adjacent areas, there was a significant increase in the number of tumor cells showing karyorrhexis. The large granular cells (LGC) contained periodic acid Schiff‐positive round granules in the cytoplasm and were stained positively for Thy‐1.2 surface antigen. The LGC were also positive for asialo GM1 surface antigen but not for Lyt‐1, Lyt‐2 or IgG surface antigens. This evidence suggests that the LGC are lymphokine‐activated killer‐like cells which were derived from a natural killer cell lineage. The concomitant increases in the number of LGC and the number of cells showing karyorrhexis in the tumors of the mice treated with rIL‐2 suggest that LGC play an important role in the destruction of tumor cells.