Research Highlights

North, Benbarche et al. engineered synthetic introns that were spliced specifically in cancer cells expressing the mutant spliceosome factor SF3B1. This led to expression of herpes simplex virus-thymidine kinase and vulnerability of cancer cells to treatment with the antiviral drug ganciclovir.

Nolan et al. used a mouse model of acute radiation exposure to reveal that radiotherapy can create a pro-metastatic lung microenvironment, an effect mediated by neutrophils.

Kobayashi et al. describe a role for silent mutations in creating functional KRAS-Q61K and develop a strategy that could potentially target this mutant as well as other RAS-Q61X mutations.

Asrir et al. show that tumour-associated high endothelial venues (TA-HEVs) in tumour-bearing mice are points of entry for lymphocytes, and increasing TA-HEVs frequency and maturation improves immune checkpoint blockade.

Kerdidani et al. have identified MHC-II-expressing cancer-associated fibroblasts in non-small-cell lung cancers where they appear to promote anti-tumour immunity.

Yang, Zhang, Luan et al. report that a germline variant that increases the risk of Philadelphia chromosome-like acute lymphoblastic leukaemia upregulates GATA3 expression, which changes chromatin accessibility to allow activation of oncogenic pathways.

Somasundara, Moss, Feigman et al. show that γδ natural killer T-like (NKT) cells expand during the late stages of pregnancy in mice because of changes in mammary epithelial cell surface protein expression, which was associated with suppressed mammary oncogenesis induced by BRCA1 loss or MYC-overexpression.

Vincze et al. have provided definitive evidence for the validity of Peto’s paradox by analysing cancer incidence in the largest study of mammal species to date.

Thandapani et al. examined the role for tRNA biogenesis in T cell acute lymphoblastic leukaemia (T-ALL), and found that T-ALL cells are sensitive to valine tRNA levels, which could be exploited therapeutically by dietary valine restriction.

Nie et al. performed metabolomics profiling on samples obtained from patients during the development of invasive lung adenocarcinoma and showed that metabolic pathways are progressively disrupted.

Hung, Yost, Xie et al. show that extrachromosomal DNAs (ecDNAs) are held together in hubs in the nucleus and that intermolecular interactions between ecDNAs can enhance oncogene expression.

Li, Xiao and colleagues show that antihistamines might increase the efficacy of immune checkpoint blockade.

Liu et al. show that glycogen accumulates in pre-malignant liver cells by undergoing liquid–liquid phase separation and, by sequestering Hippo kinases MST1 and MST2, promotes YAP-driven tumorigenesis.

Klemm et al. examined the role of tumour-associated macrophages (TAMs) at different stages of brain metastasis in mouse models and found that targeting TAMs by inhibiting both CSF1R and STAT5 might have long-lasting efficacy and prevent resistance.

Pernigoni et al. present a unique mode of non-genetic resistance accounting for castration-resistant prostate cancer that is mediated by androgen-synthesizing gut microbiota.

Neuhöfer et al. have identified a rare subpopulation of pancreatic acinar cells in the exocrine compartment that renews the pancreas by fuelling clonal expansion. When harbouring Kras mutations, these acinar cells accelerated clone formation and might represent an early cancer precursor lesion.

Canale et al. engineered the bacterial strain Escherichia coli Nissle 1917 to recycle ammonia into arginine, and showed synergistic responses with anti-programmed cell death 1 ligand 1 therapy in tumour-bearing mice when injected intratumourally or given systemically.

Two recent studies have found that both the adaptive immune system and inflammation can drive the selection of cells carrying mutations that facilitate tumour initiation.

Using zebrafish and human pluripotent stem cell-derived models of melanoma, Baggiolini, Callahan et al. demonstrate that cells expressing progenitor-like programmes and specific chromatin-modifying enzymes are more readily transformed by BRAF^V600E.

Oren et al. developed a lentiviral barcode library, called Watermelon, to characterize the rare population of cycling persister cancer cells that arise during the course of drug treatment and promote tumour relapse.