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.