Role, function and regulation of the thymocyte selection-associated high mobility group box protein in CD8+ T cell exhaustion

Cheng, Yanmin; Shao, Zhaozhao; Chen, Li; Zheng, Qiaoyu; Zhang, Qiqi; Ding, Wenjie; Zhang, Meng; Yu, Qianli; Gao, Dian

doi:10.1016/j.imlet.2020.11.004

Cited by 14 publications

(11 citation statements)

References 62 publications

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“…Recent studies revealed that TOX promotes and maintains CD8 + T cell exhaustion and the development of various cancers, including HCC. [15][16][17] TOX reduces the degradation of PD-1 and promotes the translocation of PD-1 to the surface of T cells, leading to maintain a high PD-1 expression levels. 17 These results may suggest that immune surveillance is compromised in the liver of NASH-HCC mice, contributing to the limited efficacy of ICIs.…”

Section: Impaired Tumor Immune Surveillance May Limit Efficacy Of Immunotherapy For Nash-related Hccmentioning

confidence: 99%

Does immune checkpoint inhibitor exhibit limited efficacy against non‐viral hepatocellular carcinoma?: A review of clinical trials

Eso

Taura

Seno

2021

Hepatology Research

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Immunotherapy with immune checkpoint inhibitors has been shown to be beneficial for cancers originating from various organs. In May 2020, combination therapy with anti-programmed death-ligand 1 antibody atezolizumab and anti-vascular endothelial growth factor (VEGF) antibody bevacizumab was approved as a novel firstline systemic therapy for hepatocellular carcinoma (HCC). The number of patients with HCC not caused by hepatitis virus infection (non-viral HCC), including nonalcoholic steatohepatitis (NASH)-related HCC, has been increasing in recent years. Recently, Pfister and colleagues reported that immune checkpoint inhibitors may exhibit limited efficacy against NASH-related HCC, based on basic research and clinical data. This review will discuss the mechanism of impaired tumor immune surveillance in NASH and analyze the results of previously published clinical trials of immune checkpoint inhibitors to investigate whether patients with non-viral HCC are less likely to benefit from immunotherapy with immune checkpoint inhibitors.Furthermore, we also discuss the possibility of enhancing the therapeutic effect of immune checkpoint inhibitors for NASH-related HCC by combining anti-VEGF agents.

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Section: Impaired Tumor Immune Surveillance May Limit Efficacy Of Immunotherapy For Nash-related Hccmentioning

confidence: 99%

Does immune checkpoint inhibitor exhibit limited efficacy against non‐viral hepatocellular carcinoma?: A review of clinical trials

Eso

Taura

Seno

2021

Hepatology Research

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“…TOX is transiently elevated via TCR-mediated calcineurin signaling during mouse β selection and positive selection in the thymus and reduced with the maturation of CD4 + and CD8 + T cells [ 21 , 23 ]. Moreover, recent research has suggested that TOX serves as an important transcription factor in the process of CD8 + T cell exhaustion [ 26 , 27 , 28 ], which is characterized by the decreased cytokine production and cytolytic activity of CD8 + T cells. CD8 + T cells, a kind of immune cell, accumulate in the intima of arteries in atherosclerosis [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes and Prediction of Expression Regulation Networks in Dysfunctional Endothelium

Cheng

Zeng

Zhao

et al. 2022

Genes

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The detection of early coronary atherosclerosis (ECA) is still a challenge and the mechanism of endothelial dysfunction remains unclear. In the present study, we aimed to identify differentially expressed genes (DEGs) and the regulatory network of miRNAs as well as TFs in dysfunctional endothelium to elucidate the possible pathogenesis of ECA and find new potential markers. The GSE132651 data set of the GEO database was used for the bioinformatic analysis. Principal component analysis (PCA), the identification of DEGs, correlation analysis between significant DEGs, the prediction of regulatory networks of miRNA and transcription factors (TFs), the validation of the selected significant DEGs, and the receiver operating characteristic (ROC) curve analysis as well as area under the curve (AUC) values were performed. We identified ten genes with significantly upregulated signatures and thirteen genes with significantly downregulated signals. Following this, we found twenty-two miRNAs regulating two or more DEGs based on the miRNA–target gene regulatory network. TFs with targets ≥ 10 were E2F1, RBPJ, SSX3, MMS19, POU3F3, HOXB5, and KLF4. Finally, three significant DEGs (TOX, RasGRP3, TSPAN13) were selected to perform validation experiments. Our study identified TOX, RasGRP3, and TSPAN13 in dysfunctional endothelium and provided potential biomarkers as well as new insights into the possible molecular mechanisms of ECA.

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“…TOX is required for the development of CD4+ T cells, natural killer (NK) cells and innate lymphoid cells (ILCs), as well as the autoimmunity mediated by CD8+ T cells. Emerging evidence supports role for TOX in the induction of T cell exhaustion in the setting of tumor or chronic viral infection by mediating transcriptional and epigenetic changes 6 .…”

Section: Thymocyte Selection Associated High Mobility Group Box (Tox)mentioning

confidence: 97%

Novel Biomarkers in Cutaneous T Cell Lymphomas

Przybylski¹

2022

Preprint

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Cutaneous T cell lymphomas (CTCLs) are caused by malignant clonal proliferation of skin-tropic T cells. Most patients have an indolent disease course managed with skin-directed therapies, while some entities, or in advanced stages of disease, have aggressive progression and poor survival. To efficiently treat CTCL consistent entity markers are needed to prevent the delay in diagnosis and to provide disease specific treatment to patients. Recently, the introduction of high throughput parallel sequencing methods resulted in identification of numerous genetic and ep-igenetic alterations affecting the transcriptome of CTCL cells. In this review, most relevant genes, including TOX, CADM1, PLS3, DNM3, CXCL13, PD-1, BCL11B and TMEM244 are reported that are specifically expressed in CTCL. Upon verification their specificity and sensitivity in larger studies, their altered expression will be able to be recognized as novel biomarkers, that can im-prove the early diagnosis of CTCL.

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Role, function and regulation of the thymocyte selection-associated high mobility group box protein in CD8+ T cell exhaustion

Cited by 14 publications

References 62 publications

Does immune checkpoint inhibitor exhibit limited efficacy against non‐viral hepatocellular carcinoma?: A review of clinical trials

Does immune checkpoint inhibitor exhibit limited efficacy against non‐viral hepatocellular carcinoma?: A review of clinical trials

Identification of Differentially Expressed Genes and Prediction of Expression Regulation Networks in Dysfunctional Endothelium

Novel Biomarkers in Cutaneous T Cell Lymphomas

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