title: TIM-3 expression in lymphoma cells predicts chemoresistance in patients with adult T-cell leukemia/lymphoma.
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.
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Hasita
authors.initials: H
authors.lastname: Horlad
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ohnishi
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Chaoya
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 839-0851, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Niino
authors.affiliation: Department of Pathology, School of Medicine, Kurume University, Kurume, Fukuoka 839-0851, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ohshima
authors.affiliation: Institute for Advanced Medical Research, Graduate School of Medicine, Keio University, Tokyo 108-8345, Japan.
authors.forename: Masahisa
authors.initials: M
authors.lastname: Jinushi
authors.affiliation: Institute for Virus Research, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Matsuoka
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Takeya
authors.affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komohara
keywords: TIM-3; adult T-cell leukemia/lymphoma; chemoresistance; cluster of differentiation 163; macrophage