Journal
JOURNAL OF DERMATOLOGICAL SCIENCE
Volume 96, Issue 3, Pages 134-142Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jdermsci.2019.09.004
Keywords
Cutaneous T-cell lymphoma; Galectin-9; Anti-tumor immunity; Apoptosis; T cell immunoglobulin and mucin domain 3
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Funding
- Ministry of Education, Culture, Sports, Science and Technology in Japan [26893052, 16K19709]
- Grants-in-Aid for Scientific Research [26893052, 16K19709] Funding Source: KAKEN
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Background: Galectin-9, a member of the galectin family, can promote tumor growth through inducing apoptosis in anti-tumor immune cells via T cell immunoglobulin and mucin domain 3 (TIM-3). On the other hand, galectin-9 also induces tumor cell apoptosis in many malignancies and thought to have potential as an anti-cancer agent. Objective: To examine the expression and therapeutic applicability of galectin-9 in cutaneous T-cell lymphoma (CTCL). Methods: Galectin-9 expression in lesional skin and sera was measured using CTCL samples. The effect of galectin-9 on CTCL cell lines was investigated in vitro. We also examined effect of galectin-9 on tumor growth of CTCL cells in immune-deficient mice. Moreover, we examined the efficacy of galectin-9, anti-TIM-3 blocking antibody, or their combination on tumor growth of EL-4 cells in wild-type mice. Results: Galectin-9 was expressed on tumor cells in lesional skin of CTCL and the expression levels were associated with decreased CD8(+) T-cell infiltration. Serum galectin-9 levels were correlated with disease severity markers. High-dose galectin-9 induced cell death of CTCL cell lines through activation of caspase-3 and caspase-9, independently of TIM-3. High-dose galectin-9 suppressed the growth of CTCL cells and EL-4 cells in vivo. Furthermore, additional anti-TIM-3 blocking antibody administration to galectin-9 achieved greater inhibition of tumor growth compared to single administration. Conclusion: Galectin-9 expression on tumor cells may be associated with CTCL progression through attenuating anti-tumor immunity. On the other hand, exogenous high-dose galectin-9 administration can be a therapeutic strategy for CTCL and anti-TIM-3 blocking antibody can augment the efficacy of galectin-9. (C) 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
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