David Bending
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View article: Towards active vaccination against tumour endothelial marker Robo4
Towards active vaccination against tumour endothelial marker Robo4 Open
Targeting tumour antigens is a major challenge in cancer-immunotherapy. We use active vaccination to induce antibodies targeting self-antigen Robo4, which is selectively expressed on tumour vascular endothelium, supporting vascular develop…
View article: Remote Force Modulation of the T‐Cell Receptor Reveals an NFAT‐Threshold for CD4 <sup>+</sup> T‐Cell Activation
Remote Force Modulation of the T‐Cell Receptor Reveals an NFAT‐Threshold for CD4 <sup>+</sup> T‐Cell Activation Open
Mechano‐modulation of cell surface proteins to influence cell activation has been shown as a promising new advanced therapy for regenerative medicine applications. These strategies rely on the manipulation of mechanosensitive cell surface …
View article: Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression
Stem-like memory and precursors of exhausted T cells share a common progenitor defined by ID3 expression Open
Stem-like T cells are attractive immunotherapeutic targets in patients with cancer given their ability to proliferate and differentiate into effector progeny. Thus, identifying T cells with enhanced stemness and understanding their develop…
View article: Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4+ T cell activation
Lag3 and PD-1 pathways preferentially regulate NFAT-dependent TCR signalling programmes during early CD4+ T cell activation Open
Introduction Lag3 and PD-1 are immune checkpoints that regulate T cell responses and are current immunotherapy targets. Yet how they function to control early stages of CD4+ T cell activation remains unclear. Methods Here, we show that the…
View article: Remote force modulation of the T-cell receptor reveals an NFAT-threshold for CD4<sup>+</sup>T cell activation
Remote force modulation of the T-cell receptor reveals an NFAT-threshold for CD4<sup>+</sup>T cell activation Open
/Summary Mechano-modulation of cell surface proteins to influence cell activation has been shown as a promising new advanced therapy for regenerative medicine applications. These strategies rely on the manipulation of mechanosensitive cell…
View article: LAG-3 blockade reactivates the CD8<sup>+</sup>T cell expansion program to re-expand contracted clones in the tumor
LAG-3 blockade reactivates the CD8<sup>+</sup>T cell expansion program to re-expand contracted clones in the tumor Open
Effective cancer immunotherapy relies on the clonal proliferation and expansion of CD8 + T cells in the tumor 1,2 . However, our insights into clonal expansions are limited, owing to an inability to track the same clones in tumors over tim…
View article: Vancomycin impairs macrophage fungal killing by disrupting mitochondrial morphology and function
Vancomycin impairs macrophage fungal killing by disrupting mitochondrial morphology and function Open
Vancomycin is a widely prescribed antibiotic used in the treatment of Gram-positive bacterial infections. We recently showed that this antibiotic disrupted protective anti-fungal immune responses via microbiome dysbiosis, enhancing suscept…
View article: Interferon-γ and IL-27 positively regulate type 1 regulatory T-cell development during adaptive tolerance
Interferon-γ and IL-27 positively regulate type 1 regulatory T-cell development during adaptive tolerance Open
Summary Strong T-cell receptor (TCR) and IL-27 signalling influence type-1 regulatory (Tr1) T-cell development but whether other signals determine their differentiation is unclear. Utilising Tg4 TCR transgenic mice we established a model f…
View article: Lag3 and PD-1 pathways regulate NFAT-dependent TCR signalling programmes during early CD4<sup>+</sup>T cell activation
Lag3 and PD-1 pathways regulate NFAT-dependent TCR signalling programmes during early CD4<sup>+</sup>T cell activation Open
Summary Lag3 and PD-1 are immune checkpoints that regulate T cell responses and are current immunotherapy targets. Yet how they function to control early CD4 + T cell activation remains unclear. Here, we show that the PD-1 and Lag3 pathway…
View article: The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection
The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic Trypanosoma brucei infection Open
The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system (CNS), but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular proto…
View article: Conserved developmental rewiring of the TCR signalosome drives tolerance in innate-like lymphocytes
Conserved developmental rewiring of the TCR signalosome drives tolerance in innate-like lymphocytes Open
Natural intraepithelial T lymphocytes (T-IELs) are innate-like, intestine-resident T cells essential for gut homeostasis. These cells express self-reactive T cell antigen receptors (TCRs) due to thymic agonist selection, but they do not ca…
View article: T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures
T-cell response to checkpoint blockade immunotherapies: from fundamental mechanisms to treatment signatures Open
Immune checkpoint immunotherapies act to block inhibitory receptors on the surface of T cells and other cells of the immune system. This can increase activation of immune cells and promote tumour clearance. Whilst this is very effective in…
View article: The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic<i>Trypanosoma brucei</i>infection
The murine meninges acquire lymphoid tissue properties and harbour autoreactive B cells during chronic<i>Trypanosoma brucei</i>infection Open
The meningeal space is a critical brain structure providing immunosurveillance for the central nervous system, but the impact of infections on the meningeal immune landscape is far from being fully understood. The extracellular protozoan p…
View article: Nr4a nuclear receptors: markers and modulators of antigen receptor signaling
Nr4a nuclear receptors: markers and modulators of antigen receptor signaling Open
Nr4a1-3 encode a small family of orphan nuclear hormone receptors with transcriptional activity. Their expression reflects both acute and chronic antigen-receptor signaling in T and B-cells, and they have been implicated in critical aspect…
View article: <i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity
<i>Salmonella</i>cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity Open
Summary Bacterial cancer therapy (BCT) is a promising therapeutic for solid tumours. Salmonella enterica Typhimurium (STm) is well-studied amongst bacterial vectors due to advantages in genetic modification and metabolic adaptation. A long…
View article: Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation
Succinate uptake by T cells suppresses their effector function via inhibition of mitochondrial glucose oxidation Open
Succinate dehydrogenase (SDH) loss-of-function mutations drive succinate accumulation in tumor microenvironments, for example in the neuroendocrine tumors pheochromocytoma (PC) and paraganglioma (PG). Control of innate immune cell activity…
View article: Correction: Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits
Correction: Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits Open
sponsorship: Biotechnology and Biological Sciences Research Council|BB/J013951/2
View article: Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits
Context-dependent effects of IL-2 rewire immunity into distinct cellular circuits Open
Interleukin 2 (IL-2) is a key homeostatic cytokine, with therapeutic applications in both immunogenic and tolerogenic immune modulation. Clinical use has been hampered by pleiotropic functionality and widespread receptor expression, with u…
View article: Nur77-Tempo mice reveal T cell steady state antigen recognition
Nur77-Tempo mice reveal T cell steady state antigen recognition Open
In lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell receptor (TCR) reporters. Nr4a3-Timer of cell kinetics and activity (Tocky) mice are a ground…
View article: Antigen and Checkpoint Receptor Recalibration of T Cell Receptor Signal Strength
Antigen and Checkpoint Receptor Recalibration of T Cell Receptor Signal Strength Open
Summary How T cell receptor (TCR) signal strength modulates T cell function and to what extent this is modified by immune checkpoint blockade (ICB) are key questions in immunology. Using Nr4a3-Tocky mice as a digital read-out of NFAT pathw…