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Overexpression of Interleukin-1α Suppresses Liver Metastasis of Lymphoma: Implications for Antitumor Effects of CD8+ T-cells
Journal of Histochemistry & Cytochemistry ( IF 3.2 ) Pub Date : 2021-02-09 , DOI: 10.1369/0022155421991634
Kazuhiko Udagawa 1 , Yasuo Niki 1 , Toshiyuki Kikuchi 1, 2 , Yusuke Fukuhara 1 , Yuki Takeda 1 , Takeshi Miyamoto 1, 3 , Morio Matsumoto 1 , Masaya Nakamura 1
Affiliation  

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:



中文翻译:

白细胞介素-1α的过表达抑制淋巴瘤的肝转移:CD8 + T细胞的抗肿瘤作用的影响。

白介素(IL)-1在致癌,肿瘤进展和转移中起关键作用。尽管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学贡献仍不清楚。这项研究使用了移植到人IL(hIL)-1α条件性转基因(hIL-1αcTg)小鼠中的EL4 T细胞淋巴瘤细胞的肝转移模型。hIL-1α的过量生产抑制了EL4 T细胞淋巴瘤的宏观和组织学肝转移。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,hIL-1αcTg小鼠中大量的CD8 + T细胞显示出更大的肝血管浸润。hIL-1αcTg小鼠肝脏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,细胞毒性试验表明,来自荷瘤hIL-1αcTg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,而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中起重要作用:

更新日期:2021-03-24
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