Cancer
Tumor-intrinsic response to IFNγ shapes the tumor microenvironment and anti–PD-1 response in NSCLCUsing an immunocompetent mouse model of NSCLC, this study demonstrates that tumor-intrinsic response to IFNγ determines response to anti–PD-1 through alterations in the tumor microenvironment.
A network of human functional gene interactions from knockout fitness screens in cancer cellsThe function of human genes can be strongly inferred from their knockout fitness profiles across hundreds of CRISPR screens, illuminating the modular organization of the cell.
The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical mannerPI3K and p38 act in a hierarchical manner to enhance mTORC1 activity and stress granule formation; although PI3K is the main driver, the impact of p38 gets apparent as PI3K activity declines.
Gene editing enables T-cell engineering to redirect antigen specificity for potent tumor rejectionTargeted integration of a tumor-reactive T-cell receptor into the TRAC locus using CRISPR-Cas9 and AAV6 redirects primary human T cells against tumor cells in vitro and in vivo.
Dependence on Myb expression is attenuated in myeloid leukaemia with N-terminal CEBPA mutationsWe show that for acute myeloid leukaemias with CEBPA mutations, the dependency of leukaemia growth and differentiation on the Myb transcription factor is related to the combination of N- and C-terminal mutations involved and how this affects overall gene expression.
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changesThis work demonstrates that pathogenic variants in PISD cause mitochondrial disease and suggests a novel mechanistic link whereby impaired lipid content in the inner mitochondrial membrane alters the activity of inner mitochondrial membrane proteases.
Innate extracellular vesicles from melanoma patients suppress β-catenin in tumor cells by miRNA-34aOperated cancer patients develop elevated levels of extracellular vesicles (EVs) in their blood stream, suppressing cancer cells through miRNA-34a.
Optimized ChIP-seq method facilitates transcription factor profiling in human tumorsThis study presents an optimized ChIP-seq protocol to enhance transcription factor profiling in human tumours, enabling the analysis of highly challenging samples, including core needle biopsies.
A C/EBPα–Wnt connection in gut homeostasis and carcinogenesisThis research reveals an antagonism between C/EBPα expression and activated Wnt signaling in the human and mouse gut and suggests a tumor suppressor function of C/EBPα in human and murine intestinal cancer.
Disruption of stromal hedgehog signaling initiates RNF5-mediated proteasomal degradation of PTEN and accelerates pancreatic tumor growthDisrupting paracrine Hedgehog signaling in pancreatic cancer stroma through genetic deletion of fibroblast Smoothened leads to proteasomal degradation of fibroblast PTEN and accelerates tumor growth.