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Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function

Summary of work

Using the gene-editing tool CRISPR, a research team led by PICI researcher Alexander Marson, MD, PhD, of UCSF designed a new way to evaluate thousands of genetic mutations in human T-cells at one time. This technique is called SLICE, for “single guide RNA lentiviral infection with Cas9 protein electroporation” and can quickly determine which genes may impact cellular growth, development and stimulation. In the paper, the researchers showed many possible applications for cancer immunotherapy and immunology. For example, the team found genes associated with T-cell proliferation and immunosuppression. In an experiment targeting these newly found immunosuppression-related genes, T-cells exposed to tumor cells exhibited heightened cancer-killing ability.

Why this is impactful to patients

This new CRISPR screening method provides scientists with a powerful tool to find new cancer targets and build the next generation of tumor-fighting immunotherapies. “Essentially, what SLICE does is create a faster, more reliable way to probe many different pathways that may impact T-cells, which play a central role in immunotherapy’s power to fight cancer,” said Samantha Bucktrout, PhD, director of research at PICI. “Ideally, this could lead to new and more effective immuno-oncology drugs as well as a better understanding of immune system regulation.”