SERPINE1 and SERPINB2-driven fibrin-rich niches locally programme immunosuppressive macrophages and exclude T cells, enabling spatially organized immune evasion in pancreatic ductal carcinoma.

SERPINE1 and SERPINB2-driven fibrin-rich niches locally programme immunosuppressive macrophages and exclude T cells, enabling spatially organized immune evasion in pancreatic ductal carcinoma.

Tumor-associated macrophages (TAMs), which commonly express FOLR2 or TREM2, are enriched in solid tumors and keep the tumor microenvironment (TME) imm…

Rao et al. demonstrate that convergent somatic hypermutations in the light chain, enriched within a sarbecovirus-specific public antibody clonotype, drive affinity maturation. This antibody targets a ...

Reyes-Gopar et al. introduce Stellarscope, a computational approach for quantifying locus-specific transposable element expression in single-cell RNA sequencing data. The authors profile human PBMCs a...

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Genomics; Virology

The heterogeneity of cancers is driven by diverse mechanisms underlying oncogenesis such as differential ‘cell-of-origin’ progenitors, mutagenesis, and viral infections. Classification of B-cell lymph...

The FANCD2-FANCI heterodimer contributes to DNA repair at interstrand crosslinks and sites of replication stress. This complex has been physically and mechanistically linked to double-strand break (DSB) repair, but its role in that process remains undefined. Here we show that the FANCD2-FANCI heterodimer dynamically interacts with open chromatin regions, including transient, DSB-induced open chromatin, where it can be stabilized by co-activation by the DNA repair kinase ATM and the Fanconi anemia core ubiquitin ligase. The loaded FANCD2-FANCI heterodimer stabilizes open chromatin and promotes resection and loading of RPA through increased association of BRCA1 and BLM. Chromatin-loaded FANCD2-FANCI has a second distinct function promoting a G2 arrest that is dependent on the ATR-CHK1-WEE1 axis. Our results support a two-step genome surveillance model in which FANCD2-FANCI monitors open chromatin sites and is stably loaded to coordinate DNA repair activities in response to signaling from a DNA repair kinase. ### Competing Interest Statement The authors have declared no competing interest.

Staphylococcus aureus skin infection induces eosinophil innate immune memory to exacerbate allergen-induced airway inflammation.

While highlighting the complexity and heterogeneity of tumor immune microenvironments, the application of single-cell analyses in human cancers has identified recurrent subsets of tumor-associated mac...

Regulatory T (Treg) cells are a suppressive subset of CD4+ T cells that maintain immune homeostasis and restrain inflammation. Three decades after their discovery, the promise of strategies to harness Treg cells for therapy has never been stronger. Multiple clinical trials seeking to enhance endogenous Treg cells or deliver them as a cell-based therapy have been performed and hint at signs of success, as well as to important limitations and unanswered questions. Strategies to deplete Treg cells in cancer are also in active clinical testing. Furthermore, multi-dimensional methods to interrogate the biology of Treg cells are leading to a refined understanding of Treg cell biology and new approaches to harness tissue-specific functions for therapy. A new generation of Treg cell clinical trials is now being fuelled by advances in nanomedicine and synthetic biology, seeking more precise ways to tailor Treg cell function. This Review will discuss recent advances in our understanding of human

By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promot...

ALT: two men are riding a bicycle with a basket on it .

Nature Reviews Genetics - In this Tools of the Trade article, Ankit Agrawal introduces the computational framework NiCo (Niche Covariation), which integrates spatial transcriptomics with...

In a model of pancreatic ductal adenocarcinoma, extrachromosomal DNAs are shown to be a source of high-level focal amplification driving MYC heterogeneity and phenotypic adaptation.

Phagocytosed bacteria can serve as an alternative nutrient source for macrophages, influencing their metabolic and immune responses through the recycling of microbial components, with the process regulated by nutrient-sensing mechanisms and bacterial viability.

Abstract. The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication

A freeze on "new and continuation awards" will "remain in place" pending DEI review, states a new internal memo.

How IRF7 promotes autoimmune B cell responses and systemic autoimmunity is unclear. Analysis of spontaneous SLE-prone mice deficient in IRF7 uncovered the IRF7 role in regulating autoimmune germinal center (GC), plasma cell (PC) and autoantibody responses and disease. IRF7, however, was dispensable for foreign antigen driven GC, PC and antibody responses. Competitive bone marrow (BM) chimeras highlighted the importance of IRF7 in hematopoietic cells in spontaneous GC and PC differentiation. Single-cell-RNAseq of SLE-prone B cells indicated IRF7 mediated B cell differentiation through GC and PC fates. Mechanistic studies revealed that IRF7 promoted B cell differentiation through GC and PC fates by regulating the transcriptome, translation, and metabolism of SLE-prone B cells. Mixed BM chimeras demonstrated a requirement for B cell-intrinsic IRF7 in IgG autoantibody production but not sufficient for promoting spontaneous GC and PC responses. Altogether, we delineate previously unknown B cell-intrinsic and -extrinsic mechanisms of IRF7-promoted spontaneous GC and PC responses, loss of tolerance, autoantibody production and SLE development. Summary Fike et al. describe previously unknown mechanisms by which IRF7 controls autoimmune B cell and autoantibody responses. Mechanistic studies guided by single-cell-RNAseq and ChIPseq reveal that IRF7 promotes B cell differentiation through germinal center and plasma cell fates by regulating the transcriptome, translation, and metabolism of lupus-prone B cells. ### Competing Interest Statement The authors have declared no competing interest.

Tumor-associated macrophages (TAM) enhance cancer progression by promoting angiogenesis, extracellular matrix (ECM) remodeling, and immune suppression. Nerve infiltration is a hallmark of various canc...