Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression

Dong, Jianfeng; Cheng, Lijun; Zhao, Minchao; Pan, Xiang-Feng; Feng, Zhiqiang; Wang, Dawei

doi:10.1177/1010428317701651

Cited by 12 publications

(7 citation statements)

References 28 publications

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“…TIM-3 expression is also found on CD8 + T cells, regulatory T cells (Tregs), and NK cells [50]. Furthermore, M2-like macrophages show higher levels of TIM-3 expression than M1-like macrophages [44,53]. Consistent with human expression data, TIM-3 expression on peripheral blood monocytes and tumorassociated macrophages has been shown to correlate with disease progression in a murine model of hepatocellular carcinoma [44,54].…”

Section: Tim-3supporting

confidence: 56%

TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy

Dayoub

Brekken

2020

Cell Commun Signal

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Immunotherapy for cancer is making impressive strides at improving survival of a subset of cancer patients. To increase the breadth of patients that benefit from immunotherapy, new strategies that combat the immunosuppressive microenvironment of tumors are needed. Phosphatidylserine (PS) signaling is exploited by tumors to enhance tumor immune evasion and thus strategies to inhibit PS-mediated immune suppression have potential to increase the efficacy of immunotherapy. PS is a membrane lipid that flips to the outer surface of the cell membrane during apoptosis and/or cell stress. Externalized PS can drive efferocytosis or engage PS receptors (PSRs) to promote local immune suppression. In the tumor microenvironment (TME) PS-mediated immune suppression is often termed apoptotic mimicry. Monoclonal antibodies (mAbs) targeting PS or PSRs have been developed and are in preclinical and clinical testing. The TIM (T-cell/transmembrane, immunoglobulin, and mucin) and TAM (Tyro3, AXL, and MerTK) family of receptors are PSRs that have been shown to drive PS-mediated immune suppression in tumors. This review will highlight the development of mAbs targeting PS, TIM-3 and the TAM receptors.

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Section: Tim-3supporting

confidence: 56%

TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy

Dayoub

Brekken

2020

Cell Commun Signal

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“…A combination of both IHC and PCR were used in seven studies [70][71][72][73][74][75][76], both IHC and FC in four [11,[77][78][79], and one study used a combination of IHC, PCR and FC [80]. In situ hybridization [81], immunoblotting [82], cell sorting [83] and genotyping [84] were used in a single study each, and four studies had alternative methodologies [85][86][87][88] such as computed tomography [85], tumor growth kinetics analysis [86], radiographic analysis [87], and observed treatment response [88].…”

Section: Resultsmentioning

confidence: 99%

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Kujan

Schaijik

Farah

2020

Cancers

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Cancers of the oral cavity cause significant cancer-related death worldwide. While survival rates have improved in recent years, new methods of treatment are being investigated to limit disease progression and to improve outcomes, particularly in oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD). The emerging treatment modality of immunotherapy targets immune checkpoint molecules including PD-1 and its ligand PD-L1, CTLA-4, LAG-3, and TIM-3 to enhance the host immune response against tumours, and to limit the growth and progression of cancer cells. In this systematic review, we searched five databases for keywords pertaining to oral cancers and OPMDs, along with immune checkpoint inhibitors, in order to summarize the current status of their use and efficacy in these diseases. A total of 644 different articles were identified between 2004 and 2019, with 76 deemed suitable for inclusion in the study, providing a total of 8826 samples. Combined results show expression of PD-1 and PD-L1 in the majority of OPMD and OSCC samples, with expression correlating with increased progression and decreased survival rates. Immunotherapy agents pembrolizumab and nivolumab target PD-1 and have been shown to prolong survival rates and improve disease outcomes, especially in combination with chemotherapy or radiotherapy. Despite the equivocal nature of current evidence, there is support for the prognostic and predictive value of immune checkpoint molecules, especially PD-L1, and many studies provide support for the effective use of immune checkpoint inhibitors in the management of OSCC. Limited data is available for OPMD, therefore this should be the focus of future research.

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“…scenario two, is also unlikely. CD4 + T cells have been reported to produce Gal-9 ( 37 , 38 ), but other cells such as keratinocytes and mast cells are probably much more relevant sources of Gal-9 in AD ( 24 ). As for the third and fourth options, the fact that Gal-9 levels and rates of TIM-3 + CD4 + T cells are strongly correlated suggests that the mechanisms that drive the elevation of both are shared, at least in part, rather than independent.…”

Section: Discussionmentioning

confidence: 99%

Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3

Zhang

Yang

et al. 2022

Front. Immunol.

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BackgroundAtopic dermatitis (AD), a common type 2 inflammatory disease, is driven by T helper (TH) 2/TH22polarization and cytokines.Galectin-9 (Gal-9), via its receptor T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3), can promote TH2/TH22 immunity. The relevance of this in AD is largely unclear.ObjectivesTo characterize the role of TIM-3 and Gal-9 in the pathogenesis of AD and underlying mechanisms.MethodsWe assessed the expression of Gal-9 and TIM-3 in 30 AD patients, to compare them with those of 30 healthy controls (HC) and to explore possible links with disease features including AD activity (SCORAD), IgE levels, and circulating eosinophils and B cells. We also determined the effects of Gal-9 on T cells from the AD patients.ResultsOur AD patients had markedly higher levels of serum Gal-9 and circulating TIM-3-expressing TH1 and TH17 cells than HC. Gal-9 and TIM-3 were linked to high disease activity, IgE levels, and circulating eosinophils and/or B cells. The rates of circulating TIM-3-positive CD4+ cells were positively correlated with rates of TH2/TH22 cells and negatively correlated with rates of TH1/TH17 cells. Gal-9 inhibited the proliferation and induced the apoptosis of T cells in patients with AD, especially in those with severe AD.ConclusionOur findings suggest thatGal-9, via TIM-3, contributes to the pathogenesis of AD by augmenting TH2/TH22 polarization through the downregulation of TH1/TH17immunity. This makes Gal-9 and TIM-3 interesting to explore further, as possible drivers of disease and targets of novel AD treatment.

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Tim-3-expressing macrophages are functionally suppressed and expanded in oral squamous cell carcinoma due to virus-induced Gal-9 expression

Cited by 12 publications

References 28 publications

TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy

TIMs, TAMs, and PS- antibody targeting: implications for cancer immunotherapy

Immune Checkpoint Inhibitors in Oral Cavity Squamous Cell Carcinoma and Oral Potentially Malignant Disorders: A Systematic Review

Galectin-9 contributes to the pathogenesis of atopic dermatitis via T cell immunoglobulin mucin-3

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