With the ongoing advancement of immune checkpoint research, targeting tumors through immune checkpoint blockade has emerged as a crucial approach in cancer therapy. T cell immunoglobulin and mucin-domain containing protein 3 (TIM-3) functions as a negative immune checkpoint. It has been demonstrated that the interaction of TIM-3 with its ligand galectin-9 (Gal-9) can promote immune escape in a variety of cancers. In hematologic, digestive, and respiratory tumors, it affects different signaling pathways by blocking TIM-3/Gal-9 interaction, thereby regulating the growth of T cells, B cells, dendritic cells, NK cells, and monocytes/macrophages, and inhibiting regulatory T cells to exert anti-tumor effects. TIM-3 antibodies have potential therapeutic value as immune checkpoint inhibitors in molecularly-targeted anti-tumor therapy. This article reviews the mechanisms of anti-tumor effects of TIM-3/Gal-9 in the tumor microenvironment of various cancers.

01 Nov 2022·Journal of Surgical Research

Tim-3 Blockade Decreases the Apoptosis of CD8+ T Cells and Reduces the Severity of Sepsis in Mice

Article

Author: Deng, Xiaoming ; Liu, Shanshan ; Jiang, Zhengyu ; Wang, Changli ; Bo, Lulong

INTRODUCTIONThe T cell immunoglobulin and mucin domain 3 (Tim-3) mediated immunosuppressive pathway has been shown to play an essential role in the development of sepsis. However, the influence of Tim-3 blockade during sepsis and the possible effects on T cells' function remains largely unknown. Our study investigates the role of Tim-3 in cecal ligation and puncture (CLP)-induced sepsis in mice.METHODSSepsis was induced in C57BL/6 male mice via CLP. The expression of Tim-3 in CD8⁺ T cells after CLP challenge was measured. A dose of 50 μg anti-Tim-3 antibodies was injected intraperitoneally 30 min after surgery. Postoperative survival, bacterial clearance in the blood and peritoneal lavage ﬂuid, cytokine secretion in the blood, and lung and liver histology were evaluated. In addition, the apoptosis of immune cells in the spleen and thymus was examined, respectively.RESULTSTim-3 expression was elevated in the splenic CD8⁺ T cells of septic mice. At the early stage of CLP-induced sepsis, blocking Tim-3 with anti-Tim-3 antibodies reduced the severity of sepsis. The anti-Tim-3 antibodies alleviated the morphology of lung and liver injuries in septic mice. The anti-Tim-3 antibodies also reduced the severity of the inflammatory responses and lymphocyte apoptosis in septic mice.CONCLUSIONSAnti-Tim-3 antibodies might be a potential therapeutic strategy for sepsis.

01 Dec 2019·Journal of Dermatological Science

Possible therapeutic applicability of galectin-9 in cutaneous T-cell lymphoma

Article

Author: Oka, Tomonori ; Sato, Shinichi ; Kamijo, Hiroaki ; Nakajima, Rina ; Sugaya, Makoto ; Miyagaki, Tomomitsu ; Suga, Hiraku ; Shishido-Takahashi, Naomi

BACKGROUNDGalectin-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.OBJECTIVETo examine the expression and therapeutic applicability of galectin-9 in cutaneous T-cell lymphoma (CTCL).METHODSGalectin-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.RESULTSGalectin-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.CONCLUSIONGalectin-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.

100 Deals associated with NB-0893

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	Canada	Northern Biologics, Inc.	-

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