Publications by authors named "G Apriamashvili"
Article Synopsis
- The study explores how the PD-1 immune checkpoint protein is regulated on CD8 T cells, aiming to find ways to lower its abundance without hindering T cell activation, which is crucial for effective cancer therapy.
- Researchers conducted a CRISPR-Cas9 screen on murine CD8 T cells to identify genes impacting PD-1 levels, discovering that inhibiting the TMED protein family, especially TMED10, could reduce PD-1 on the cell surface and enhance T cell function.
- The findings highlight a new regulatory mechanism for PD-1 and suggest that targeting TMED could be a promising therapeutic strategy to improve T cell responses in cancer treatment, as indicated by correlations in mouse models and patient survival data.
Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction.
View Article and Find Full Text PDFFunctional genetic screens by CRISPR-Cas9 allow for the unbiased discovery of proteins causally involved in complex biological processes. In recent years, this approach has been used by multiple laboratories to uncover a range of tumor cell regulators determining immune sensitivity. In this review, we provide an overview of genetic screens carried out both and .
View Article and Find Full Text PDFTumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8 T cell antitumor activity. Although innate natural killer (NK) cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both innate and adaptive immune elimination, we performed parallel genome-wide CRISPR-Cas9 knockout screens under NK and CD8 T cell pressure.
View Article and Find Full Text PDFThe cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation of its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators of IFNγ-R1 cell surface abundance, we identify STUB1 as an E3 ubiquitin ligase for IFNγ-R1 in complex with its signal-relaying kinase JAK1.
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