Publications by authors named "Erin A Brunazzi"
Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown.
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- Researchers are exploring ways to reverse or limit the lack of regulatory T cells (Tregs) to improve immunotherapy for autoimmune diseases like type 1 diabetes.
- In a study of NOD mice, Tregs found in the pancreas (intraislet Tregs) showed a dysfunctional phenotype, lacking a key receptor called neuropilin-1 (Nrp1), which is essential for Treg stability and function.
- Restoring Nrp1 expression in Tregs demonstrated a protective effect against the onset of autoimmune diabetes, suggesting that maintaining Nrp1 signaling could be a potential strategy for addressing Treg deficiencies in autoimmune diseases.
Impaired chronic viral and tumor clearance has been attributed to CD8 T cell exhaustion, a differentiation state in which T cells have reduced and altered effector function that can be partially reversed upon blockade of inhibitory receptors. The role of the exhaustion program and transcriptional networks that control CD8 T cell function and fate in autoimmunity is not clear. Here we show that intra-islet CD8 T cells phenotypically, transcriptionally, epigenetically and metabolically possess features of canonically exhausted T cells, yet maintain important differences.
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- CD4 T cells and CD8 T cells share similar developmental pathways, but mature CD4 Tconv cells do not have distinct markers, making them hard to differentiate from T regulatory cells.
- Researchers created a specialized mouse line that allows for targeted gene manipulation in CD4 Tconv cells while preserving the function of CD4 Treg cells, a process termed allele conditioning.
- These engineered mouse strains are valuable tools for studying gene function in CD4 T cells, especially in relation to immune responses and diseases like melanoma.
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- TRAIL is an immune molecule essential for regulating cell death in tumors and autoimmune diseases, but understanding its exact functions has been challenging due to inadequate models.* -
- Researchers created a conditional knockout in mice to investigate TRAIL's role specifically in regulatory T cells, finding that its deletion did not alter tumor growth or T cell function in tested models.* -
- This study suggests TRAIL may not be the primary mechanism for T cell suppression in tumors or autoimmune diseases, although it could still play a role alongside other factors; the new mouse model will aid further research.*
Regulatory T (Treg) cells are crucial for immune homeostasis, but they also contribute to tumor immune evasion by promoting a suppressive tumor microenvironment (TME). Mice with Treg cell-restricted Neuropilin-1 deficiency show tumor resistance while maintaining peripheral immune homeostasis, thereby providing a controlled system to interrogate the impact of intratumoral Treg cells on the TME. Using this and other genetic models, we showed that Treg cells shaped the transcriptional landscape across multiple tumor-infiltrating immune cell types.
View Article and Find Full Text PDFRegulatory T cells (T) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral T stability and function but is dispensable for peripheral immune tolerance. T-restricted Nrp1 deletion results in profound tumor resistance due to T functional fragility.
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