Inducible T‐cell co‐stimulator: Signaling mechanisms in T follicular helper cells and beyond

Panneton, Vincent; Chang, Jinsam; Witalis, Mariko; Li, Joanna; Suh, Woong‐Kyung

doi:10.1111/imr.12771

Cited by 42 publications

(34 citation statements)

References 138 publications

(278 reference statements)

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“…Further, B cells express complement receptors 1 and 2 (CR1/CR2) that engage for optimal antibody production (Gottschalk & Kurts, 2015). Follicular helper cells sample and retain antigen also in a complement‐receptor‐dependent fashion (Panneton, Chang, Witalis, Li, & Suh, 2019). It is now undisputed that complement and its receptors are fine‐tuning and shaping adaptive immune responses.…”

Section: Complement and Hypertensionmentioning

confidence: 99%

The role of complement in arterial hypertension and hypertensive end organ damage

Wenzel

Kemper

Bode

2020

British J Pharmacology

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Increasing evidence indicates that hypertension and hypertensive end organ damage are not only mediated by haemodynamic injury but that inflammation also plays an important role. The complement system protects the host from a hostile microbial environment and maintains tissue and cell integrity through the elimination of altered or dead cells. As an important effector arm of innate immunity, it plays also central roles in the regulation of adaptive immunity. Thus, complement activation may drive the pathology of hypertension through its effects on innate and adaptive immune responses, aside from direct effects on the vasculature. Recent experimental data strongly support a role for complement in all stages of arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical haemolytic uraemic syndrome suggest also a role for complement in the development of malignant nephrosclerosis. Here, we review the role of complement in hypertension and hypertensive end organ damage. Linked Articles This article is part of a themed issue on Canonical and non‐canonical functions of the complement system in health and disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.14/issuetoc

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Section: Complement and Hypertensionmentioning

confidence: 99%

The role of complement in arterial hypertension and hypertensive end organ damage

Wenzel

Kemper

Bode

2020

British J Pharmacology

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“…T cells CD8, T cells CD4 memory activated, and T cells follicular helper were negatively correlated with risk level, while macrophages M0 and mast cells activated were positively correlated with risk level. plasma cells, T cells CD8, T cells CD4 memory activated, and T cells follicular helper were reported to play important roles in inhibiting tumors ( Kim and Cantor, 2014 ; Wouters and Nelson, 2018 ; Panneton et al, 2019 ), while macrophages and mast cells activated have been proved to be associated with tumor metastasis and poor prognosis ( Komohara et al, 2016 ; Zhang et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Establishment and Validation of a Comprehensive Prognostic Model for Patients With HNSCC Metastasis

Shen

et al. 2021

Front. Genet.

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ObjectiveTo identify biomarkers related to head and neck squamous cell carcinoma (HNSCC) metastasis and establish a prognostic model for patients with HNSCC.MethodsHNSCC mRNA expression data of metastasis and non-metastatic samples were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. After screening the differentially expressed genes (DEGs) in the two datasets, a prognostic model, including clinical factors and biomarkers, was established, and verified in 36 samples of HNSCC by quantitative real-time transcription (qRT)-PCR. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene sets enrichment analysis (GSEA) were consulted to explore the functions of the DEGs.ResultsIn total, 108 DEGs were identified. GSEA, GO, and KEGG analyses showed that these DEGs were mainly involved in the proliferation and metastasis of HNSCC. Six genes that were significantly related to metastasis, immune cell infiltration and prognosis were further identified to construct a prognostic gene signature. The reliability of the gene signature was verified in 36 samples of HNSCC. A prognostic model, including tumor stage, risk level, and a nomogram for prediction were further established. Receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), C-index, and calibration plots showed that the model and nomogram perform well.ConclusionWe constructed a six-gene signature and a nomogram with high performance in predicting the prognosis of patients with HNSCC metastasis.

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“…Important examples are provided by the remarkable improvements in disease outcome obtained with antibodies targeting CTLA-4 and PD1 [37][38][39][40] . ICOS, a member of this family, has emerged as a promising target for immunotherapy [24][25][26][27][28][29][30] because of its central role in the T/B-cell co-signaling pathway 3 associated with adaptive and innate immunity 21,41 .…”

Section: Discussionmentioning

confidence: 99%

Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies

et al. 2020

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The inducible co-stimulator (ICOS) is a member of the CD28/B7 superfamily, and delivers a positive co-stimulatory signal to activated T cells upon binding to its ligand (ICOS-L). Dysregulation of this pathway has been implicated in autoimmune diseases and cancer, and is currently under clinical investigation as an immune checkpoint blockade. Here, we describe the molecular interactions of the ICOS/ICOS-L immune complex at 3.3 Å resolution. A central FDPPPF motif and residues within the CC’ loop of ICOS are responsible for the specificity of the interaction with ICOS-L, with a distinct receptor binding orientation in comparison to other family members. Furthermore, our structure and binding data reveal that the ICOS N110 N-linked glycan participates in ICOS-L binding. In addition, we report crystal structures of ICOS and ICOS-L in complex with monoclonal antibodies under clinical evaluation in immunotherapy. Strikingly, antibody paratopes closely mimic receptor-ligand binding core interactions, in addition to contacting peripheral residues to confer high binding affinities. Our results uncover key molecular interactions of an immune complex central to human adaptive immunity and have direct implications for the ongoing development of therapeutic interventions targeting immune checkpoint receptors.

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Inducible T‐cell co‐stimulator: Signaling mechanisms in T follicular helper cells and beyond

Cited by 42 publications

References 138 publications

The role of complement in arterial hypertension and hypertensive end organ damage

The role of complement in arterial hypertension and hypertensive end organ damage

Establishment and Validation of a Comprehensive Prognostic Model for Patients With HNSCC Metastasis

Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies

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