CTLA-4: From mechanism to autoimmune therapy

Hosseini, Abdolkarim; Gharibi, Tohid; Marofi, Faroogh; Babaloo, Zohreh; Baradaran, Behzad

doi:10.1016/j.intimp.2020.106221

Cited by 188 publications

(112 citation statements)

References 269 publications

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“…Previous researches have confirmed that biologics targeting immune checkpoints, such as abatacept, which targets the CTLA-4 related immune checkpoint, have high potential for clinical application in treating autoimmune diseases (19). However, abatacept has not demonstrated any efficacy in PBC; no biochemical responses or improved clinical outcomes were observed during treatment (20), indicating that the excessive autoimmune response in PBC might be due to other immune checkpoints.…”

Section: Discussionmentioning

confidence: 99%

Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis

Deng

Fei

et al. 2020

Front. Immunol.

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The relationship between the cluster of differentiation 226 (CD226)/T cell Ig and ITIM domain (TIGIT) immune checkpoint and primary biliary cholangitis (PBC) pathogenesis is unknown. Herein, PBC patients (n = 42) showed significantly higher proportions of peripheral CD8 + T and CD4 + T cells expressing either CD226 or TIGIT than disease (n = 25) and healthy (n = 30) controls. The percentage of CD8 + TIGIT + T cell was negatively associated with total bilirubin, direct bilirubin, total bile acid, γ-glutamyl transpeptidase, and alkaline phosphatase, but positively correlated with platelet count; alkaline phosphatase was positively associated with the frequency of CD8 + CD226 + T cell; and the CD226/TIGIT ratio of CD8 + T cell was positively associated with total bilirubin, direct bilirubin, total bile acid, γ-glutamyl transpeptidase, alkaline phosphatase, and aspartate aminotransferase to platelet ratio, but negatively correlated with albumin and platelet count. The effector function of CD8 + CD226 + T cells was more robust than the CD8 + CD226 − counterparts. CD226 blockade reduced CD107a + , IFN-γ + , and TNF-α + proportions among CD8 + CD226 + T cells, inhibiting CD8 + T cell proliferation. In conclusion, CD226/TIGIT immune checkpoint imbalance is involved in the pathogenesis of PBC. The CD226/TIGIT ratio of CD8 + T cell is a potential biomarker for evaluating the disease status and the prognosis of PBC patients. Moreover, CD8 + CD226 + T cells represent a possible therapeutic target for PBC, and blocking CD226 could inhibit the activity of this cell subset in vitro.

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Section: Discussionmentioning

confidence: 99%

Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis

Deng

Fei

et al. 2020

Front. Immunol.

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“…CTLA-4 is an important co-inhibitory receptor on T-cells that downregulates T-cell activation and induces tolerance [ 24 ]. It is transiently expressed following T-cell activation and blocks the costimulatory effect of constitutively expressed CD28 by competing with CD28 for CD80 binding [ 25 ]; it then inhibits Akt activation by recruiting PP2A [ 26 , 27 ].…”

Section: Immune Checkpoints and Their T-cell Inactivation Pathwaysmentioning

confidence: 99%

Immune Checkpoints in Viral Infections

Cai

Liu

Zhong

et al. 2020

Viruses

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As evidence has mounted that virus-infected cells, such as cancer cells, negatively regulate the function of T-cells via immune checkpoints, it has become increasingly clear that viral infections similarly exploit immune checkpoints as an immune system escape mechanism. Although immune checkpoint therapy has been successfully used in cancer treatment, numerous studies have suggested that such therapy may also be highly relevant for treating viral infection, especially chronic viral infections. However, it has not yet been applied in this manner. Here, we reviewed recent findings regarding immune checkpoints in viral infections, including COVID-19, and discussed the role of immune checkpoints in different viral infections, as well as the potential for applying immune checkpoint blockades as antiviral therapy.

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“…Cytotoxic T-lymphocyte antigen 4 (CTLA4) is homologous to CD28 and similarly binds to CD80 or CD86, preventing the attachment of CD28 to these surface proteins. In other words, CTLA4 is a negative regulatory molecule of T cell activation [22,23]. The pharmacologic inhibition of CTLA4 is one of the possible approaches employed in cancer immunotherapy [22].…”

Section: Immunotherapy In Clinical Practicementioning

confidence: 99%

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

Sajjadi¹,

Venetis²,

Scatena³

et al. 2020

ecancer

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Precision immunotherapy is a crucial approach to improve the efficacy of anti-cancer treatments, particularly in the metastatic setting. In this respect, accurate patient selection takes advantage of the multidimensional integration of patients' clinical information and tumourspecific biomarkers status. Among these biomarkers, programmed death-ligand 1, tumourinfiltrating lymphocytes, microsatellite instability, mismatch repair and tumour mutational burden have been widely investigated. However, novel tumour-specific biomarkers and testing methods will further improve patients' outcomes. Here, we discuss the currently available strategies for the implementation of a precision immunotherapy approach in the clinical management of metastatic solid tumours and highlight future perspectives.

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CTLA-4: From mechanism to autoimmune therapy

Cited by 188 publications

References 269 publications

Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis

Imbalance of the CD226/TIGIT Immune Checkpoint Is Involved in the Pathogenesis of Primary Biliary Cholangitis

Immune Checkpoints in Viral Infections

Biomarkers for precision immunotherapy in the metastatic setting: hope or reality?

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