TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma
TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma
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DOI：
10.3892/ol.2016.4774
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发表时间：
2016-08-01
期刊：
影响因子：
2.9
通讯作者：
Komohara, Yoshihiro
中科院分区：
文献类型：
--
作者：
Horlad, Hasita;Ohnishi, Koji;Komohara, Yoshihiro
成人T细胞白血病/淋巴瘤（ATLL）是一种侵袭性恶性淋巴瘤，对化疗具有高度耐药性。然而，ATLL的化学抗性的详细机制尚未阐明。我们先前证明巨噬细胞和淋巴瘤细胞之间的直接细胞-细胞相互作用与ATLL患者的淋巴瘤进展显著相关。本研究的目的是进一步分析巨噬细胞和ATLL细胞之间的细胞-细胞相互作用的影响，通过细胞培养研究和免疫组化分析，使用人类ATLL样本。发现与巨噬细胞直接共培养在ATLL ATN-1细胞系中诱导化学抗性，但在其它细胞系（包括TL-Mor、艾德和ATL-2S）中不诱导化学抗性。还发现，通过与巨噬细胞长期共培养，在ATN-1细胞中诱导T细胞IG和含粘蛋白结构域的分子-3（TIM-3）的表达。TIM-3基因转染可诱导ATN-1细胞产生耐药性。免疫组化染色显示25例ATLL组织中有TIM-3表达。尽管TIM-3表达与总生存率或T分类无关，但与化疗耐药相关。因此，TIM-3表达被认为是预测化疗疗效的标志物，TIM-3相关信号可能是ATLL患者的治疗靶点。
Adult T-cell leukemia/lymphoma (ATLL), an aggressive type of malignant lymphoma, is highly resistant to chemotherapy. However, the detailed mechanisms of the chemoresistance of ATLL have never been elucidated. We previously demonstrated that direct cell-cell interaction between macrophages and lymphoma cells was significantly associated with lymphoma progression in patients with ATLL. The present study aimed to further analyze the effects of cell-cell interaction between macrophages and ATLL cells by means of cell culture studies and immunohistochemical analysis using human ATLL samples. It was found that direct co-culture with macrophages induced chemoresistance in the ATLL ATN-1 cell line, but not in other cell lines, including TL-Mor, ED and ATL-2S. It was also found that expression of the T cell Ig and mucin domain-containing molecule-3 (TIM-3) was induced in ATN-1 cells by their long-term co-culture with macrophages. TIM-3 gene transfection induced chemoresistance in the ATN-1 cells. Immunostaining of ATLL tissues showed TIM-3 expression in 25 out of 58 ATLL cases. Although TIM-3 expression was not associated with overall survival or T classification, it was associated with resistance to chemotherapy. TIM-3 expression is therefore considered to be a marker for predicting the efficacy of chemotherapy, and TIM-3-associated signals may be a therapeutic target for patients with ATLL.