BTLA/HVEM Signaling: Milestones in Research and Role in Chronic Hepatitis B Virus Infection

Yu, Xueping; Zheng, Yijuan; Mao, Richeng; Su, Zhijun; Zhang, Jiming

doi:10.3389/fimmu.2019.00617

Cited by 58 publications

(35 citation statements)

References 76 publications

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“…BTLA (CD272) is identified as another inhibitory receptor that belongs to CD28 superfamily [113]. It is located on human chromosome 3 in q13.2 and encodes a 289-amino acid type I glycosylated transmembrane protein [25]. Similar to PD-1 and CTLA-4, the protein structure of BTLA includes a single extracellular region, a transmembrane domain and cytoplasmic domain.…”

Section: Newly Emerging Immune Checkpointsmentioning

confidence: 99%

“…Thus, intensive researches aimed at finding novel immune checkpoint targets have been ongoing. The next generation immune checkpoints such as lymphocyte activation gene-3 (LAG-3) [20], T cell immunoglobulin and mucin-domain containing-3 (TIM-3) [21], T cell immunoglobulin and ITIM domain (TIGIT) [22], V-domain Ig suppressor of T cell activation (VISTA) [23], B7 homolog 3 protein (B7-H3) [24] and B and T cell lymphocyte attenuator (BTLA) [25] demonstrate as promising therapeutic targets with the chance to realize clinical application. In this review, we will emphasize these newly-characterized immune checkpoint molecules and their clinical studies that suggest the promising future for the clinical application.…”

Section: Introductionmentioning

confidence: 99%

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Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4

et al. 2019

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The emergence of immune checkpoint inhibitors (ICIs), mainly including anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) monoclonal antibodies (mAbs), has shaped therapeutic landscape of some type of cancers. Despite some ICIs have manifested compelling clinical effectiveness in certain tumor types, the majority of patients still showed de novo or adaptive resistance. At present, the overall efficiency of immune checkpoint therapy remains unsatisfactory. Exploring additional immune checkpoint molecules is a hot research topic. Recent studies have identified several new immune checkpoint targets, like lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoglobulin and ITIM domain (TIGIT), V-domain Ig suppressor of T cell activation (VISTA), and so on. The investigations about these molecules have generated promising results in preclinical studies and/or clinical trials. In this review, we discussed the structure and expression of these newly-characterized immune checkpoints molecules, presented the current progress and understanding of them. Moreover, we summarized the clinical data pertinent to these recent immune checkpoint molecules as well as their application prospects.

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Section: Newly Emerging Immune Checkpointsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4

et al. 2019

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“…Soon thereafter, CD160 was found to also inhibit T cell function, binding to the same ligand [ 223 ]. Both Ig-superfamily receptors (BTLA and CD160) inhibit T cell functions, and together with the stimulatory ligand LIGHT (binding to HVEM) form part of an intricate, bidirectional signalling network (BTLA, CD160, LIGHT, HVEM) [ 224 ].…”

Section: Extrinsic Mediators Of T Cell Exhaustionmentioning

confidence: 99%

Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion

Verdon

Mulazzani

Jenkins

2020

IJMS

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T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically “exhausted” in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

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“…on multiple cells, such as T, B, natural killer, dendritic and myeloid cells (6). Furthermore, the lung, liver and kidneys have been reported to express HVEM (7). In addition to BTLA, HVEM is also a ligand for CD160, and the TNF superfamily members LIGHT and lymphotoxin-β (6).…”

Section: Clinical Significance Of Herpes Virus Entry Mediator Expressmentioning

confidence: 99%

Clinical significance of herpes virus entry mediator expression in hepatitis B virus‑related hepatocellular carcinoma

Gao

et al. 2020

Oncol Lett

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Herpes virus entry mediator (HVEM) is overexpressed in several malignancies, including hepatocellular carcinoma (HCC). However, to the best of our knowledge, the clinical significance of HVEM in hepatitis B virus (HBV)-related HCC remains unclear. Thus, the present study aimed to explore the clinical significance of HVEM in HBV-related HCC. In the present study, HVEM expression was evaluated in HCC cell lines and HCC frozen samples. The prognostic value of HVEM was assessed in a cohort of 221 patients with HBV-related HCC, following radical resection. Band T-lymphocyte attenuator (BTLA) expression in subsets of CD8 + T cells was determined via flow cytometry analysis. The results demonstrated high HVEM expression in HCC cell lines, and in HCC tissues compared with paired non-cancerous liver tissues. HVEM expression was demonstrated to be significantly associated with tumor encapsulation and vascular invasion. Furthermore, tumor HVEM status was significantly associated with infiltration of regulatory T cells, but not with CD8 + T cells. Notably, high HVEM expression in HCC was determined to be an independent predictor of an unfavorable outcome of patients with HCC following radical resection. Higher BTLA expression (the receptor of HVEM) was observed in both HCC-infiltrating CD8 + effector memory (CCR7-CD45RA-) and CD45RA + effector memory (CCR7-CD45RA +) T cells in HCC tissues and blood compared with those in paired peritumor tissues or peripheral blood. Taken together, the results of the present study suggest that HVEM may serve a critical role in HBV-related HCC, most likely by promoting tumor progression and tumor immune evasion, thus the HVEM/BLTA signaling pathway may be a potential target in tumor immunotherapy.

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BTLA/HVEM Signaling: Milestones in Research and Role in Chronic Hepatitis B Virus Infection

Cited by 58 publications

References 76 publications

Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4

Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4

Cellular and Molecular Mechanisms of CD8+ T Cell Differentiation, Dysfunction and Exhaustion

Clinical significance of herpes virus entry mediator expression in hepatitis B virus‑related hepatocellular carcinoma

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