Search

A population of TRAIL-positive astrocytes in glioblastoma contributes to an immunosuppressive tumour microenvironment and this mechanism can be targeted with an engineered oncolytic virus to improve outcomes.

Inhibition of the fatty acid oxidation metabolic pathway through inactivation of Cpt1b enhances cardiomyocyte survival and proliferation and allows heart regeneration in adult mice.

Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytomas are characterized by a scarcity of T cells, but their phenotypes and functionality are lesser known. Here authors provide an integrative approach to describe the immune microenvironment of these tumors and show that gemistocytic tumor cells, a cell type abundant in the tumor stroma surrounding perivascular T cell accumulations, generate a glial scarring-like functional state, responsible for T cell exclusion.

Weaver and colleagues show that TGFβ-induced collagen deposition and metabolic reprogramming of the breast cancer microenvironment by tumor-associated macrophages restrict the antitumor activity of CD8⁺ T cells in female breast cancer.

Using animal models and clinical samples, the authors report that glioblastoma metabolites activate the transcription factor aryl hydrocarbon receptor in tumor-associated macrophages to modulate their function and T cell immunity, promoting tumor growth.

Inhibition of the tricarboxylic acid cycle enzyme fumarate hydratase leads to deregulation of cytokine production in macrophages, which has implications in human diseases such as systemic lupus erythematosus.

Biochemical and lipidomic analyses identify an anti-ferroptotic function of vitamin K and reveal ferroptosis suppressor protein 1 (FSP1) as the enzyme mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle.

Structural and biochemical studies of the β-barrel-assembly machinery from Flavobacterium johnsoniae reveal a subunit composition and assembly that are distinct from those of the canonical Escherichia coli complex.

Bisphenol A is used in the production of many plastic products, but has adverse health effects and is therefore being replaced. Here the authors show that its substitute, fluorene-9-bisphenol, is released from commercial plastic bottles into drinking water, and has anti-oestrogenic effects in mice.

Single-cell profiling and fate-mapping experiments in the developing brain of mice and humans show that microglia and meningeal macrophages originate from a common prenatal precursor, but that perivascular macrophages are derived postnatally from meningeal macrophages.

Blanpain and colleagues use mouse models of activated Hedgehog signalling to analyse the temporal gene expression changes involved in basal cell carcinoma initiation. They show that tumour initiation involves activation of the Wnt pathway and reprogramming of the adult interfollicular epidermis tumour-initiating cells into a cell fate resembling that of embryonic hair follicle progenitor cells.

Elevated IL-33 levels have been correlated with metastasis and poor prognosis. Here the authors show in mouse tumour xenograft models that PDGF-BB produced by tumour cells induces IL-33 via Sox7 in tumour pericytes, and IL-33 promotes metastasis through its effects on tumour-associated macrophages.

Inhibitors of the BET family proteins are limited by their potency and oral bio-availability. Here, the authors report a new BET inhibitor, NHWD-870, with improved potency compared to previous BET inhibitors, and show that it suppresses BRD4 and targets tumour associated macrophages.

The origin and source of mammary gland progenitors and how they interact with the adipose‐rich stroma is unclear. Here, the authors identify PDGFRα⁺ adipocyte progenitors in the murine mammary stroma as a mesenchymal cell lineage recruited into the expanding epithelium during development, hormone exposure and pregnancy.

The risk of developing cancer increases with age. Here, the authors address the contribution of age-dependent accumulation of senescent cells within the tumour stroma compartment and show that senescent cells increase the infiltration of myeloid-derived suppressor cells that inhibit cytotoxic T-cells, thus facilitating tumour outgrowth.

The TAM family of receptor tyrosine kinases exerts pleiotropic functions in health and disease. Here, the authors show that TAM receptors control osteoblastic bone formation and identified MERTK as a novel target for bone anabolic therapy and mitigation of bone metastasis including its associated osteolytic bone disease

Osteoarthritis (OA) leads to joint degeneration, including the progressive loss of articular cartilage. Here the authors show that kindlin-2 expression is decreased in degenerate cartilage and that its overexpression decelerates the progression of OA in mice.

Nuclear architecture depends on proper regulation of lamin A/C modifications. Here, the authors show that TAF4A and NF-Y control Kansl2 expression in muscle stem cells, preserving genome stability and supporting muscle regeneration.

The interaction of tumour-associated macrophages (TAMs) with cancer and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. The authors of this Review examine the diversity of TAMs in various cancer indications, which is being revisited with the advent of single-cell technologies, and discuss the functional roles of different TAM states, the prognostic and predictive value of TAM-related signatures as well as approaches involving TAMs that are currently being or will soon be tested in clinical trials.

Bernier, Hefendehl et al. describe a stromal progenitor cell population consisting of pericytes, venular smooth muscle cells and perivascular fibroblasts in the adult brain that modify their function and coordinate blood vessel repair following stroke.

Pharmaceuticals derived from benzylisoquinoline alkaloids find application in modern medicine. Here, the authors report the design of a parallel enzymatic cascade to generate halogenated benzylisoquinoline alkaloids, that included engineering of tyrosinase mutants to enhance substrate capabilities.

Drug-loaded nanoparticles allow controlled release and enhanced delivery, yet understanding in vivobehavior has been difficult. Here, the authors develop a platinum prodrug coupled to a polymer platform, and use intravital imaging to show that the nanoparticle accumulates in macrophages, from the which drug redistributes to neighboring tumour cells.

The TAM tyrosine kinases, Axl and MerTK, have been implicated in rheumatoid arthritis (RA). Here, using a synovial tissue bioresource of patients with RA, the authors describe how Axl and MerTK expression and function are linked to synovial histopathology, disease activity, and therapeutic intervention with IL-6 inhibitors.

The components of the glioma immune microenvironment and their roles in promoting tumourigenesis remain poorly understood. Here, the use of single-cell RNA sequencing and multiplexed tissue-imaging in adult and pediatric high-grade gliomas reveals the activity and spatial organization of the immunomodulatory purinergic signaling pathway.

Several strategies have been attempted to target immune suppressive populations in the tumor microenvironment. Here the authors show that folate receptor β-targeted CAR-T cells eliminate immunosuppressive tumor associated macrophages, promoting endogenous antitumor immune responses and adoptive T-cell therapy in pre-clinical models.

A study demonstrates that metabolic signalling and inflammatory cues associated with obesity selectively induce expression of PD-1 on tumour-associated macrophages to suppress anti-tumour immunity.

Tissue-resident macrophages are derived from yolk sac progenitors but how and when these progenitors enter is unclear. Here the authors use fate mapping and intravital microscopy to track the movement of resident macrophage precursors from the yolk sac to fetal tissues during development.

Improved imaging techniques are required to help advance our understanding of the complex role of the tumour microenvironment (TME). Here, the authors develop a high-throughput, highly multiplexed tissue visualisation workflow and demonstrate its utility by characterising the response of the TME to radiotherapy in preclinical models of glioblastoma.

The Sonic Hedgehog subgroup of medulloblastoma are characterised by the high infiltration of tumour-associated macrophages (TAMs). Here, the authors show that TAM numbers in patients are associated with better prognosis and that, consistently, in a murine model of medulloblastoma, these TAMs have anti-tumoural properties.

The immunocytokine NHS-IL12 is targeted to necrotic tumour areas to prompt an immune response. Authors show here in mouse colon and breast models that the combination of histone deacetylase inhibitor, Entinostat, and NHS-IL12 generates a tumour microenvironment that favours tumour resolution.

STING is a promising drug target, but selective activation is necessary for safety and efficacy. Researchers have developed a two-component prodrug system for potent pharmacological activation of STING that offers excellent tumour targeting.

Inflammatory monocytes are identified as important players in T cell restimulation in the tumour microenvironment.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

On wounding, scar formation in mammals arises causing no hair follicle regeneration, but it is unclear if scarring precludes regeneration. Here, the authors show that if Sonic hedgehog signaling is activated in the wound, an inductive dermal niche forms, enabling regeneration and hair follicle formation.

Tamoxifen, widely used to modulate oestrogen receptor activity in breast cancer treatment, also regulates sphingolipid metabolism. Here the authors show that the latter activity of tamoxifen stimulates pro-inflammatory and antibacterial activities of human neutrophils.

An inherently explainable AI trained on 1,015 expert-annotated prostate tissue images achieved strong Gleason pattern segmentation while providing interpretable outputs and addressing interobserver variability in pathology.

Presence of peritoneal metastasis is associated with a decreased survival in patients with colorectal cancer. Here, the authors show that peritoneal-resident macrophages promote the formation of an immunosuppressive environment that facilitate peritoneal metastasis in colorectal cancer.

Adam, Yang et al. show that the transcription factors NFIB and NFIX promote stemness by establishing chromatin accessibility and regulating the super-enhancers that govern bulge stem cell identity.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

Genetic screening identifies a rich catalogue of regulators of micronucleus formation.

Hot carrier transport in organic systems has remained elusive due to rapid energy relaxation and limited transport properties. Here highly mobile hot carriers and their relaxation dynamics are reported in a crystalline two-dimensional conjugated coordination polymer, revealing two distinct transport regimes.

Emergence of ABL1 kinase inhibitor resistant clones may cause disease relapse in Philadelphia chromosome-positive acute lymphoblastic leukemia. Here, the authors show interleukin 7 receptor (IL7R) signaling to contribute to this resistance mechanism, and that targeting the IL7R pathway may suppress incurable drug-resistant leukemia forms.