Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Wu, Fenghua; Yuan, Ye; Liu, Dong; Zhang, Lei; Song, Chang Yong; Liu, Yanyan; Li, Bo; Huang, Bo; Feng, Z M; Zhang, Guimei

doi:10.3892/or_00000909

Cited by 18 publications

(3 citation statements)

References 28 publications

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“…Wu et al (37) showed that, in mice, Tim-3 is also expressed on vascular endothelial cells (ECs), but does not function as a Gal-9 receptor on these cells, and, instead, mediates the interaction of ECs with tumor cells or T cells. For example, Tim-3 on ECs, by binding to a putative receptor on B16 tumor cells, resulting in NF-κB activation, Bcl-2 and Bcl-xL upregulation, and Bax downregulation, which finally leads to tumor cell resistance to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

et al. 2013

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Tim-3 was initially identified on activated Th1, Th17, and Tc1 cells and induces T cell death or exhaustion after binding to its ligand, Gal-9. The observed relationship between dysregulated Tim-3 expression on T cells and the progression of many clinical diseases has identified this molecule as an important target for intervention in adaptive immunity. Recent data have shown that it also plays critical roles in regulating the activities of macrophages, monocytes, dendritic cells, mast cells, natural killer cells, and endothelial cells. Although the underlying mechanisms remain unclear, dysregulation of Tim-3 expression on these innate immune cells leads to an excessive or inhibited inflammatory response and subsequent autoimmune damage or viral or tumor evasion. In this review, we focus on the expression and function of Tim-3 on innate immune cells and discuss (1) how Tim-3 is expressed and regulated on different innate immune cells; (2) how it affects the activity of different innate immune cells; and (3) how dysregulated Tim-3 expression on innate immune cells affects adaptive immunity and disease progression. Tim-3 is involved in the optimal activation of innate immune cells through its varied expression. A better understanding of the physiopathological role of the Tim-3 pathway in innate immunity will shed new light on the pathogenesis of clinical diseases, such as autoimmune diseases, chronic viral infections, and cancer, and suggest new approaches to intervention.

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Section: Introductionmentioning

confidence: 99%

Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

et al. 2013

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“…The engagement of a non-galectin 9 putative receptor on B16 melanoma cells with endothelial cell-expressed Tim-3 triggers the NF-κB signaling pathway in B16 cells. The activated NF-κB signaling augments the proliferation and resistance to apoptosis through upregulating the Bcl-2 and Bcl-xL and downregulating the Bax in these tumor cells and promotes the formation of metastatic nodules in the lung [82].…”

Section: Tim-3mentioning

confidence: 99%

Varied functions of immune checkpoints during cancer metastasis

Safarzadeh

Alizadeh

Beyranvand

et al. 2020

Cancer Immunol Immunother

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Immune checkpoints comprise diverse receptors and ligands including costimulatory and inhibitory molecules, which play monumental roles in regulating the immune system. Immune checkpoints retain key potentials in maintaining the immune system homeostasis and hindering the malignancy development and autoimmunity. The expression of inhibitory immune checkpoints delineates an increase in a plethora of metastatic tumors and the inhibition of these immune checkpoints can be followed by promising results. On the other hand, the stimulation of costimulatory immune checkpoints can restrain the metastasis originating from diverse tumors. From the review above, key findings emerged regarding potential functions of inhibitory and costimulatory immune checkpoints targeting the metastatic cascade and point towards novel potential Achilles’ heels of cancer that might be exploited therapeutically in the future.

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“…TIM-3 could activate the NF-κB signaling pathway to promote tumor cell metastasis (137). In patients or animal tumor models with chronic HIV infection, the expression of TIM-3 on T cells was significantly high (138, 139). On CD8+TILs, TIM-3 often expressed together with PD-1.…”

Section: Tim-3 (T Cell Immunoglobulin and Mucin-domain Containing-3)mentioning

confidence: 99%

The Common Costimulatory and Coinhibitory Signaling Molecules in Head and Neck Squamous Cell Carcinoma

et al. 2019

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Head and neck squamous cell carcinomas (HNSCCs) are closely linked with immunosuppression, accompanied by complex immune cell functional activities. The abnormal competition between costimulatory and coinhibitory signal molecules plays an important role in the malignant progression of HNSCC. This review will summarize the features of costimulatory molecules (including CD137, OX40 as well as CD40) and coinhibitory molecules (including CTLA-4, PD-1, LAG3, and TIM3), analyze the underlying mechanism behind these molecules' regulation of the progression of HNSCC, and introduce the clinic application. Vaccines, such as those targeting STING while working synergistically with monoclonal antibodies, are also discussed. A deep understanding of the tumor immune landscape will help find new and improved tumor immunotherapy for HNSCC.

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Endothelial cell-expressed Tim-3 facilitates metastasis of melanoma cells by activating the NF-κB pathway

Cited by 18 publications

References 28 publications

Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells

Varied functions of immune checkpoints during cancer metastasis

The Common Costimulatory and Coinhibitory Signaling Molecules in Head and Neck Squamous Cell Carcinoma

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