Tim-3, Lag-3, and TIGIT

Joller, Nicole; Kuchroo, Vijay K.

doi:10.1007/82_2017_62

Cited by 119 publications

(120 citation statements)

References 139 publications

(276 reference statements)

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“…In fact, LAG‐3 binds MHC II with higher affinity than the CD4 molecule. LAG‐3 also binds gal‐3 expressed by liver or tumor cells . In human CD4 + and CD8 + T cells, LAG‐3 functions as a negative regulator of T‐cell activation …”

Section: The Regulation Of Ics During Acute Hbv and Hcv Infectionsmentioning

confidence: 94%

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Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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Summary The function of T cells is tightly controlled by positive and negative regulations to ensure both successful pathogen elimination and limitation of immune‐mediated pathology. One of the mechanisms to negatively regulate the magnitude and duration of effector T cells is the expression of inhibitory checkpoint molecules (ICs) on the surface membrane of T cells. During acute viral infections, expression of these molecules is upregulated to limit the effector functions following T‐cell activation. The expression is subsequently downregulated following viral clearance. In contrast, these molecules are continuously expressed in virus‐specific T cells found in persistently infected patients, including cases of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV). The continuously high expression of ICs is responsible for the dysfunctional states of HBV‐ and HCV‐specific T cells in chronic phases, known as T‐cell exhaustion. Hence, understanding the regulation of their expression is essential to give insight into pathogenesis as well as the development of effective immune‐based antiviral therapies. This review discusses recent updated research on expression of ICs during acute and chronic phases of HBV and HCV infections as well as during the clinical course of antiviral therapy.

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Section: The Regulation Of Ics During Acute Hbv and Hcv Infectionsmentioning

confidence: 94%

“…LAG-3 also binds gal-3 expressed by liver or tumor cells. 50 In human CD4 + and CD8 + T cells, LAG-3 functions as a negative regulator of T-cell activation. 51 In a mouse model of acute LCMV infection, conflicting data were found on LAG-3 expression.…”

Section: Lag-3 Btla and Other Icsmentioning

confidence: 99%

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Hakim

Rahmadika

Jariah

2019

Reviews in Medical Virology

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“…To functionally address the relevance of the TIGIT pathway in UC NK cells, we analyzed degranulation of primary NK cells upon stimulation with MHC‐I negative, CD155‐expressing K562 target cells in the presence or absence of blocking antibodies against TIGIT or CD226. TIGIT and CD226 are both engaged by CD155 in trans , whereby CD226 transmits a stimulatory signal and TIGIT transmits an inhibitory signal into NK cells . Accordingly, treatment with a blocking anti‐TIGIT antibody resulted in a minor but significant increase of NK cell degranulation while blocking of CD226 significantly inhibited NK cell degranulation (Fig.…”

Section: Resultsmentioning

confidence: 92%

High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis

et al. 2019

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Immune checkpoints are regulators of immune cells and play key roles in the modulation of immune responses. The role of checkpoints in autoimmune disease is poorly understood but likely to be central since checkpoint inhibition during cancer treatment can cause autoimmunity. We generated a high‐dimensional single‐cell proteomics data set from PBMCs of healthy individuals and patients with ulcerative colitis (UC) by mass cytometry, enabling systems‐wide analyses of immune cell frequencies and cell type‐specific expression patterns of 12 immune checkpoints. Subtle but significant changes in immune cell frequencies and checkpoint expression were observed between UC patients on different treatment regimens and between patients and healthy controls. Most strikingly, UC patients showed a reduced number of peripheral NK‐cells and those cells showed an altered phenotype including increased TIGIT expression. Based on these results, we modulated NK‐cell function ex vivo through targeting of TIGIT pathway members. In summary, we describe a pattern of changes in immune cell abundance and checkpoint expression as a basis for UC patient stratification and we show modulation of a corresponding immune cell subset through checkpoint targeting. Our approach can be used for the identification of pathogenic immune cell subsets and guide target selection in autoimmunity and chronic inflammation.

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“…In the models of mouse and human tumors, using the antibodies of HAVCR2 can rescue the exhausted T cells [56, 57] , revealing that HAVCR2 was associated with exhaustion of CD8+ T cell. Moreover, the inhibitory receptor encoded by gene TIGIT acts as T cell intrinsic inhibitor with its ligand CD155 by restraining effector cell activation and proliferation, leading to the decreased effector function and cytokine production [58] , and the knockdown of TIGIT can revert the decreased production of cytokines [59] . TIGIT was upregulated in the exhausted cells according to our study, showing its potential key role in the exhaustion of CD8+ T cells.…”

Section: Discussionmentioning

confidence: 99%

Single cell transcriptome analysis reveals RGS1 as a new marker and promoting factor for T cell exhaustion in multiple cancers

Bai

Chen

et al. 2019

Preprint

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1 4 3 1 immunity. We summarized the putative interrelated mechanisms of above key genes identified in this 3 2 study by integrating the reported knowledge. Furthermore, we explored the heterogeneous and 3 3 preference of exhausted CD8+ T cells in each patient and found only one exhausted sub-cluster existed 3 4in the most of patients, especially in CRC and HCC. As far as we know, this is the first time to study 3 5 the mechanism of T cell exhaustion with the data of single-cell RNA sequencing of multiple cancers. 6Our study may facilitate the understanding of the mechanism of T cell exhaustion, and provide a new 3 7 way for functional research of single-cell RNA sequencing data across cancers.3 8

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Tim-3, Lag-3, and TIGIT

Cited by 119 publications

References 139 publications

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

Expressions of inhibitory checkpoint molecules in acute and chronic HBV and HCV infections: Implications for therapeutic monitoring and personalized therapy

High‐dimensional single‐cell proteomics analysis identifies immune checkpoint signatures and therapeutic targets in ulcerative colitis

Single cell transcriptome analysis reveals RGS1 as a new marker and promoting factor for T cell exhaustion in multiple cancers

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