A5053828549- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Calcium signaling and nucleotide metabolism
- Immune cells in cancer
- Cytomegalovirus and herpesvirus research
- Adenosine and Purinergic Signaling
- Synthesis and Biological Evaluation
Technion – Israel Institute of Technology
2023-2025
A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% patients metastatic melanoma 1,2 . T cell exhaustion, resulting from chronic antigen exposure tumour microenvironment, a major driver ICB resistance 3 Here, we show that CD38, an ecto-enzyme involved nicotinamide adenine dinucleotide (NAD + ) catabolism, highly expressed exhausted CD8 cells and associated resistance. Tumour-derived CD38 hi are dysfunctional,...
Abstract T cell exhaustion is a major driver of immune checkpoint blockade (ICB) resistance and clinically effective strategies to prevent or reverse restore ICB sensitivity are lacking. CD38, an ecto-enzyme involved in NAD+ catabolism, highly expressed exhausted CD8+ cells human melanoma, yet its role remains be elucidated. Here we show that CD38+CD8+ enriched during tumor progression following unsuccessful treatment strongly associated with melanoma. Chronic TCR activation type I...
Metabolism of immune cells in the tumor microenvironment (TME) plays a critical role cancer patient response to checkpoint inhibitors (ICI). Yet, metabolic characterization TME patients treated with ICI is lacking. To bridge this gap we performed semi-supervised analysis ∼1700 genes using single-cell RNA-seq data > 1 million from ∼230 samples ICI. When clustering based on their gene expression, found that similar immunological cellular states are different states. Most importantly,...
<h3>Background</h3> Terminally exhausted CD8+ T cells, resulting from chronic antigen exposure in the tumor microenvironment, are defined by loss of effector function, decreased proliferative potential, and associated with limited response to immune checkpoint blockade (ICB).<sup>1</sup> CD38 is an ecto-enzyme, involved NAD+ catabolism.<sup>2</sup> that was shown be expressed terminally cells melanoma correlate lack ICB,<sup>3</sup> although its specific role cell exhaustion therapeutic...
Despite the crucial role of T cell clones in anti-tumor activity, their characterization and association with clinical outcome following immune checkpoint inhibitors (ICI) is lacking. Here we analyzed paired single-cell RNA-sequencing/T-cell receptor sequencing 767,606 cells from 460 samples spanning 6 cancer types. We found a robust signature response based on expanded CD8+> that differentiates between responders non-responders. Analysis persistent showed transcriptional changes are...
Abstract Metabolism of immune cells in the tumor microenvironment (TME) plays a critical role cancer patient response to checkpoint inhibitors (ICI). Yet, metabolic characterization TME patients treated with ICI is lacking. To bridge this gap we performed semi-supervised analysis ∼1700 genes using single-cell RNA-seq data >1 million from ∼230 and blood samples ICI. When clustering based on their gene expression, found that similar immunological states are different states. Most...