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)-1α conditional transgenic (hIL-1α cTg) mice. Overproduction of hIL-1α suppressed both macroscopic and histological liver metastasis of EL4 T-cell lymphoma. The hIL-1α-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-1α cTg mice than in control wild-type mice. Terminal deoxynucleotidyl transferase dUTP nick-end labeling staining of liver tissue from hIL-1α 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-1α cTg mice correlated with cytotoxicity against EL4. In summary, IL-1α suppresses lymphoma metastasis, and IL-1α-activated CD8+ T-cells may play important roles in inhibiting both tumor metastasis and metastatic tumor growth:

白细胞介素 (IL)-1 在癌变、肿瘤进展和转移中起关键作用。虽然 IL-1 可能增强 CD8+ T 细胞的扩增，但 IL-1 激活的 CD8+ T 细胞对肿瘤转移的病理贡献仍不清楚。本研究使用移植到人 IL (hIL)-1α 条件性转基因 (hIL-1α cTg) 小鼠中的 EL4 T 细胞淋巴瘤细胞的肝转移模型。hIL-1α 的过量产生抑制了 EL4 T 细胞淋巴瘤的肉眼和组织学肝转移。hIL-1α 诱导的炎症状态增加了转移性肿瘤内部和周围的 CD8+ T 细胞数量。此外，与对照野生型小鼠相比，在 hIL-1α cTg 小鼠中，更多数量的 CD8+ T 细胞显示出更大的肝血管浸润。来自 hIL-1α cTg 小鼠的肝组织的末端脱氧核苷酸转移酶 dUTP 缺口末端标记染色表明肿瘤中细胞的凋亡增加。凋亡细胞的定位类似于 CD8+ T 细胞的定位。此外，细胞毒性测定显示来自荷瘤 hIL-1α cTg 小鼠的 CD8+ T 细胞计数与针对 EL4 的细胞毒性相关。总之，IL-1α 抑制淋巴瘤转移，IL-1α 激活的 CD8+ T 细胞可能在抑制肿瘤转移和转移性肿瘤生长方面发挥重要作用：