Search

N-glycans on glycoRNAs prevent innate immune sensing of endogenous small RNAs, and the natural mechanism they use demonstrates how glycoRNAs exist on the cell surface and in the endosomal network without inducing autoinflammatory responses.

Damage-associated molecular patterns (DAMPs) are released during necrotic cell death and contribute to driving inflammation. Rathinam and colleagues show that galectin-1 is a new DAMP that functions by inhibiting the receptor phosphatase CD45.

Guanylate-binding proteins (GBPs) induced by type I interferon signaling cause lysis of Francisella bacteria that have reached the host-cell cytosol. The liberated bacterial DNA is then sensed by the cytosolic AIM2 inflammasome, which activates caspase-1 and leads to pyroptotic cell death.

Kumari et al. show that host-derived extracellular vesicles capture systemic LPS and transfer it to the cytosol of immune cells via CD14-dependent endocytosis, triggering caspase-11-mediated gasdermin D activation and pyroptosis.

Comprehensive immunity requires that cells sense intracellular pathogens. In their Review, Shao and colleagues describe mechanisms for the recognition of intracellular lipopolysaccharide and its essential role in responses to Gram-negative bacteria.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

Wang and colleagues show that in skeletal muscle cells and cardiomyocytes, the glucose transporter GLUT4 is a negative regulator of RIG-I-like receptor signaling during viral infection by redistributing RIG-I and MDA5 to the plasma membrane and attenuating interferon responses.

Host-cell detection of lipopolysaccharide in the outer membrane of Gram-negative bacteria was thought to be restricted to the cell-surface receptor TLR4. It emerges that lipopolysaccharide can also be sensed in the cytoplasm.

Many pathogens induce a type I interferon response via a pathway dependent on the kinase TBK1 and transcription factor IRF3. However, LRRFIP1, a cytosolic sensor of DNA and RNA, triggers interferon production by a β-catenin-dependent signal.

Innate immune evasion is a key aspect of bacterial pathogenesis. Here, Ta et al identify and characterise EhaF, a bacterial autotransporter that functions to inhibit host innate immunity and promote the colonisation and pathogenesis of enterohemorrhagic Escherichia coli.

The authors report the cryogenic electron microscopy structures of human GSDMB in complex with Shigella IpaH7.8 and the GSDMB pore, shedding light on the molecular mechanisms of Shigella IpaH7.8 recognition and targeting of GSDMs and GSDMB pore formation.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Autophagy is a physiological process that involves the engulfment and degradation of organelles. Choi and colleagues demonstrate that autophagy is important for the removal of damaged mitochondria and thus the control of inflammation.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

The NLRP3 inflammasome is primarily known for producing inflammatory cytokines and inducing pyroptosis. Stuart and colleagues identify an additional role for NLRP3 in driving down the pH of phagosomes.

Chronic infections can result in harmful production of the proinflammatory cytokine IL-1 generated via the NLRP3 inflammasome. Sassetti et al. demonstrate that IL-1 activated by Mycobacteria results in nitrosylation and consequent regulation of the NLRP3 inflammasome.

The AIM2 inflammasome induces maturation of the proinflammatory cytokines IL-1β and IL-18. Using AIM2-deficient mice, Fitzgerald and colleagues and Alnemri and colleagues show that the AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

The mouse pathogenCitrobacter rodentium has long been used as a model for investigating the pathogenesis of the important enteric human pathogens, enterohaemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli(EPEC). In this Review, Frankel and colleagues discuss the infection cycle of this pathogen, the mucosal immune response that is elicited and the role of the gut microbiota in preventing colonization.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.

TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

Pulmonary venous tumor cells disseminating before tumor resection are heterogeneous, predict relapse and seed future metastasis of lung cancer

Ghorani et al. use a multiomics approach to characterize the effect of tumour mutational burden on the differentiation of CD4 and CD8 T cell subpopulations in non-small cell lung cancer.

Multiregion spatial histology, exome and transcriptome data from patients with non-small cell lung cancer suggest that cancer subclones from immune cold regions diversify later than subclones from immune hot regions