TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

Horlad,Hasita; Ohnishi,Koji; Ma,Chaoya; Fujiwara,Yukio; Niino,Daisuke; Ohshima,Koichi; Jinushi,Masahisa; Matsuoka,Masao; Takeya,Motohiro; Komohara,Yoshihiro

doi:10.3892/ol.2016.4774

TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma

Authors:
- Hasita Horlad
- Koji Ohnishi
- Chaoya Ma
- Yukio Fujiwara
- Daisuke Niino
- Koichi Ohshima
- Masahisa Jinushi
- Masao Matsuoka
- Motohiro Takeya
- Yoshihiro Komohara
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Affiliations: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860‑8556, Japan, Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 839‑0851, Japan, Institute for Advanced Medical Research, Graduate School of Medicine, Keio University, Tokyo 108‑8345, Japan, Institute for Virus Research, Kyoto University, Kyoto 606-8501, Japan
Published online on: June 23, 2016 https://doi.org/10.3892/ol.2016.4774
Pages: 1519-1524

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Abstract

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.

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