Overexpression Of Interleukin-1 Alpha Suppresses Liver Metastasis Of Lymphoma: Implications For Antitumor Effects Of Cd8+T-Cells

Interleukin (IL)-1 plays a key role in carcinogenesis, tumor progression, and metastasis. Although IL-1 may enhance the expansion of CD8+ T-cells, the pathological contribution of IL-1-activated CD8+ T-cells to tumor metastasis remains unclear. This study used a liver metastasis model of the EL4 T-cell lymphoma cells transplanted into human IL (hIL)-1 alpha conditional transgenic (hIL-1 alpha cTg) mice. Overproduction of hIL-1 alpha suppressed both macroscopic and histological liver metastasis of EL4 T-cell lymphoma. The hIL-1 alpha-induced inflammatory state increased the number of CD8+ T-cells both within and around metastatic tumors. Moreover, larger numbers of CD8+ T-cells showed greater infiltration of liver blood vessels in hIL-1 alpha cTg mice than in control wild-type mice. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining of liver tissue from hIL-1 alpha cTg mice indicated increased apoptosis of cells in the tumor. Localization of apoptosis cells resembled that of CD8+ T-cells. In addition, cytotoxicity assay showed that CD8+ T-cell counts from tumor-bearing hIL-1 alpha cTg mice correlated with cytotoxicity against EL4. In summary, IL-1 alpha suppresses lymphoma metastasis, and IL-1 alpha-activated CD8+ T-cells may play important roles in inhibiting both tumor metastasis and metastatic tumor growth: