Recent massively-parallel approaches to decipher gene regulatory circuits have focused on the discovery of either -regulatory elements (CREs) or -acting factors. Here, we develop a scalable approach that pairs - and -regulatory CRISPR screens to systematically dissect how the key immune checkpoint is regulated. In human pancreatic ductal adenocarcinoma (PDAC) cells, we tile the locus using ∼25,000 CRISPR perturbations in constitutive and IFNγ-stimulated conditions.
View Article and Find Full Text PDFImmune checkpoint blockade (ICB) has transformed the treatment of metastatic cancer but is hindered by variable response rates. A key unmet need is the identification of biomarkers that predict treatment response. To address this, we analyzed six whole exome sequencing cohorts with matched disease outcomes to identify genes and pathways predictive of ICB response.
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