TIM3 comes of age as an inhibitory receptor

Wolf, Yochai; Anderson, Ana C.; Kuchroo, Vijay K.

doi:10.1038/s41577-019-0224-6

Cited by 687 publications

(597 citation statements)

References 157 publications

(214 reference statements)

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“…TIM3 has been reported to have multiple ligands including galectin 9, phosphatidylserine, CEACAM1 and HMGB1. Among these ligands, HMGB1 is a necrosis-related ligand [28] . The nuclear DNA-binding protein HMGB1 binds to TIM3 and induces phagocytosis by recruiting macrophages and dendritic cells [29] .…”

Section: Resultsmentioning

confidence: 99%

TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer

Kato

Jinnouchi

Tuyukubo

et al. 2021

Translational Oncology

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Highlights Multi-IF analysis was performed to identify novel prognostic biomarker for advanced RCC patients treated with anti-PD-1 therapy. The strongest prognostic factor of response to anti-PD-1 therapy was identified as TIM3 expression on tumor cells. Patients with TIM3-positive tumor cells showed significantly longer OS and PFS than those with TIM3-negative tumor cells.

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Section: Resultsmentioning

confidence: 99%

TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer

Kato

Jinnouchi

Tuyukubo

et al. 2021

Translational Oncology

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“…Increasing evidence showed the vital role of the interaction of TIM3 and galectin-9 in several chronic diseases, such as cancer, hepatitis, and autoimmune diseases [ 8 , 9 ]. The physiological role of TIM3 has been implicated in both stimulatory and inhibitory functions [ 10 , 11 ]. The biological effect of TIM3 has been controversially discussed because of its costimulatory and coinhibitory properties.…”

Section: Introductionmentioning

confidence: 99%

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

Sun

Zou

Ding

et al. 2020

Journal of Diabetes Research

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Aims. Obesity is highly associated with type 2 diabetes mellitus (T2DM). The TIM3/galectin-9 pathway plays an important role in immune tolerance. Herein, we aimed to investigate the expression of TIM3 and galectin-9 in peripheral blood and to evaluate their clinical significance in patients with obesity and obesity-related T2DM. Methods. We performed flow cytometry on peripheral blood samples from healthy donors (HC), patients with simple obesity (OB), and patients with obesity comorbid T2DM (OD). The expression of TIM3 on CD3+, CD4+, and CD8+ T cells was determined. The level of galectin-9 in plasma was detected by ELISA. Results. We demonstrated the enhancement of TIM3 on CD3+, CD4+, and CD8+ T cells in the OB group when compared with healthy controls, while it was decreased significantly in the OD group. The TIM3+CD8+ T cells of the OB group were positively correlated with risk factors including BMI, body fat rate, and hipline. The concentration of galectin-9 of the OD group in plasma was significantly higher than that of healthy donors and the OB group. Moreover, the level of galectin-9 of the OD group was positively correlated with fasting insulin and C-peptide, which were two clinical features that represented pancreatic islet function in T2DM. Conclusions. Our results suggested that TIM3 and galectin-9 may be potential biomarkers related to the pathogenesis of obesity-related T2DM.

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“…TIM-3 recognizes galectin-9, phospholipid phosphatidylserine (PtdSer), alarmin high mobility group box 1 (HMGB1) and carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) via its Ig-like extracellular domain [117][118][119][120]. Although the intracellular tail of TIM-3 contains five tyrosines that are conserved between humans and mice and are potential phosphorylation sites, they don't conform to known binding motifs [121]. TIM-3 is expressed by NK cells and is reported to not only inhibit NK cell cytotoxicity [122], but also mediate IFNγ production [123].…”

Section: Non-mhc-i Recognizing Receptorsmentioning

confidence: 99%

Natural Killer Cells: Tumor Surveillance and Signaling

Guzman

Keating

Nicholson

2020

Cancers

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Natural killer (NK) cells play a pivotal role in cancer immunotherapy due to their innate ability to detect and kill tumorigenic cells. The decision to kill is determined by the expression of a myriad of activating and inhibitory receptors on the NK cell surface. Cell-to-cell engagement results in either self-tolerance or a cytotoxic response, governed by a fine balance between the signaling cascades downstream of the activating and inhibitory receptors. To evade a cytotoxic immune response, tumor cells can modulate the surface expression of receptor ligands and additionally, alter the conditions in the tumor microenvironment (TME), tilting the scales toward a suppressed cytotoxic NK response. To fully harness the killing power of NK cells for clinical benefit, we need to understand what defines the threshold for activation and what is required to break tolerance. This review will focus on the intracellular signaling pathways activated or suppressed in NK cells and the roles signaling intermediates play during an NK cytotoxic response.

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TIM3 comes of age as an inhibitory receptor

Cited by 687 publications

References 157 publications

TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer

TIM3 expression on tumor cells predicts response to anti-PD-1 therapy for renal cancer

Circulating T Cells Exhibit Different TIM3/Galectin-9 Expression in Patients with Obesity and Obesity-Related Diabetes

Natural Killer Cells: Tumor Surveillance and Signaling

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