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The restriction of appropriate tumour-specific antigens is a current limitation for T cell-engaging immunotherapy. Here, the authors have designed a new system constituted by two halve antibodies, which engage T cells once binding to two different antigens, to specifically eliminate double positive cells in preclinical leukemia and breast cancer mouse models.

The regulation and direction of CD4⁺ T cells into phenotypic and functional lineages is coordinated by a complex set of mechanisms. Here the authors show a role for Aiolos as a regulator of the CD4⁺ cytotoxic and T follicular helper lineages.

Enhanced IL-1β signaling pathway causes hematopoietic stem cell (HSC) to differentiate into myeloid cells and contributes to malignant hematopoiesis. Here the authors reveal that HSC differentiation is controlled by balanced levels of IL-1 receptor antagonist (IL-1rn) and IL-1β under steady-state, and that IL-1rn protects against pre-leukemic myelopoiesis by repressing IL-1β signaling.

DNA barcoding methods for the analysis of clonal heterogeneity in cancer have been limited in terms of throughput and practical requirements. Here, the authors develop SunCatcher, a rapid and sensitive barcoding approach for live single-cell clonal evolution analysis, and use this method to study breast cancer cell populations.

Chemotherapy resistance in recurrent gliomas is a large hurdle for successful therapy. Here, the authors show that some recurrent gliomas harbour O-6-methylguanine-DNA methyltransferase (MGMT) genomic rearrangements, and in vitro and in vivo these contribute to temozolomide resistance.

Circadian rhythms are known to impact a range of biological processes including in the immune system. Here the authors show how circadian rhythms modulate the T cell response to vaccination via regulation of dendritic cell metabolism.

The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.

De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, the authors show that Cul3 is essential to regulate neuronal migration by tightly regulating Plastin3 (Pls3). Pls3 cell-autonomously regulates cell migration by regulating the actin cytoskeleton organization.

Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.

Splicing factor PTBP1 is reported to promote oncogenic functions in glioblastoma (GBM). Here the authors show splicing factor SON upregulates PTBP1 expression while supresses its paralog PTBP2 through alternative splicing and the inhibition of SON reduces GBM stemness and growth.

Dick and colleagues identify human LT-HSC subsets with distinct quiescent states. They link these differences to INKA1-mediated downregulation of the transmembrane protein CD112 and its interaction with the protein deacetylase SIRT1. INKA1 is inversely correlated with the histone H4K16Ac mark, which then distinguishes ‘latent’ CD112^lo LT-HSCs from CD112^hi LT-HSCs that are more readily activated in response to hematopoietic stress.

Hydrogen peroxide attracts immune cells and induces wound inflammation. Evans et al. show that hydrogen peroxide also leads to the production of thymosin β4–sulfoxide in zebrafish wounds and in mouse hearts after myocardial infarction, where it acts as an anti-inflammatory factor that promotes wound healing.

Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks⁺ island develop a distinct mutational signature associated with colorectal cancer.

Myoepithelial cells prevent tumour growth and invasion in DCIS. Here, the authors show that p63 and TCF7 cooperate to regulate a transcription factor network for the maintenance of normal myoepithelial function and altered expression of these genes perturb myoepithelial function in DCIS to promote invasive progression.

Dietary extracellular vesicles (EVs) could potentially be absorbed by the intestinal tract of the host and exert multiple phenotypic changes. Here, the authors isolate and characterize EVs from raw and commercial bovine milk and show orally administered EVs to have a context specific role in promoting or suppressing primary tumor growth and metastasis in multiple mouse tumor models.

Signal transduction and gene expression regulation via downstream transcription factors shape the early mammalian embryo. Here the authors show that Wnt/TCF7L1 transcriptional repressive activity is required for primitive endoderm lineage formation.

The circadian clock affects immune responses, but its role in influenza infection is not well understood. Here, Sengupta et al. show that time of infection and the circadian clock have no effect on lung virus titers, but affect inflammation, morbidity and mortality.

The mechanisms by which measles virus infection induces transient immune suppression in humans are poorly understood. Here, Laksono and colleagues characterise the pathogenesis of measles-associated immune suppression in unvaccinated children, and shed new light on the long-term effects of measles on the host.

In contrast to the larynx of mammals, birds produce sound using a unique vocal organ called the syrinx. Using ex vivo preparations, Elemans et al.show that, despite large anatomical differences, sound production across a range of avian taxa is via the myoelastic-aerodynamic mechanism, the same mechanism involved in human speech.

An analysis of human papillomavirus (HPV)-specific CD8 T cells in patients with head and neck cancer identifies functional PD-1⁺TCF-1⁺CD8 T cells in the tumour with implications for therapeutic vaccination and PD-1 directed immunotherapy.

MAIT cells are abundant in the lungs and confer protection against bacterial pathogens. Whilst activation of these cells has been described during viral infections, here van Wilgenburg and colleagues show that in a murine model MAIT cells contribute to the protective host immune response to influenza virus infection.

Vpu prevents HIV superinfection and immune activation by modulating DNA repair mechanisms, particularly by inhibiting homologous repair. Vpu achieves this by disrupting the RanBP2–RanGAP1*SUMO1–Ubc9 complex at the nuclear pore to reduce PML SUMOylation and consequent PML nuclear body formation, which hampers the homologous recombination factors Rad52 and BLM.

In vitro studies in human cell lines and in vivo studies in a hamster model show that the SARS-CoV-2 Omicron variant is less pathogenic than both the Delta variant and an ancestral strain of SARS-CoV-2.

The lipopolysaccharide of the intracellular pathogen Shigella, in particular its O antigen, interacts with caspases and blocks their activation to prevent apoptosis.

Invertebrates are key components in the ecological functioning of tropical forests. Here, Ewers et al. show that, compared to primary forest, logging halves the contribution of invertebrate species to several key ecosystem processes, including litter decomposition.

Stem cell-mediated regenerative medicine requires the development of defined culture systems for the maintenance of human embryonic stem cells. Here, feedback system control is used to identify a combination of three small molecule inhibitors that enables long-term human embryonic stem cell maintenance.

The angiopoietins regulate vascular maturation, angiogenesis and lymphangiogenesis via their Tie receptors that were long believed to be endothelium-specific. Here the authors show that angiopoietins activate and control pericyte function through pericyte-expressed Tie2 triggering of Calpain, Akt and FOXO3A signalling cascades.

Integrated studies of matched tissue sites and cell types in COVID-19 patients are important to define the immune mechanisms of pathology. Here, the authors describe an immune signature in fatal COVID-19 patients harmonizing single-cell RNA sequencing of blood and matched BAL cells with deep clinical, immunological and functional data.

CD8⁺ T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.

BAFF is an important cytokine for B cell survival, and is a therapeutic target for autoimmune disorders. Here the authors show that a 'flap' region of BAFF converts BAFFR binding events into survival signals and, with structural data, that this ‘flap’ differentially modulates binding of drugs such as belimumab or atacicept.

The physiological role of crosstalk between mesenchymal stem cells (MSC) and macrophages is unclear. Here, Phinney et al. show that MSCs transfer mitochondria to macrophages under oxidative stress, and desensitize macrophages to mitochondria by using microvesicles to repress Toll receptor signalling.

T regulatory (Treg) cells can differentiate into effector Treg (eTreg) cells that might be functional in inflammatory diseases. Using RNA sequencing and epigenetic profiling, the authors show that eTreg signatures in juvenile idiopathic arthritis joints are similar to tumour microenvironment (TME) Treg cells and are affected by tissue-specific epigenetic regulation.

Histone deacetylase (HDAC) inhibitors, a class of cancer therapeutics, cause thrombocytopenia via an unknown mechanism. Here, the authors show that HDAC6 inhibition impairs proplatelet formation in human megakaryocytes, and show that this is linked to hyperacetylation of the actin-binding protein cortactin.

The role of neutrophils in cancer development is not widely appreciated. Here, the authors show that NF-κB-deficient hepatocytes overproduce chemokines, leading to hepatocellular carcinoma due to excessive neutrophil recruitment, and that neutrophil depletion prevents liver cancer in these mice.

Fluid shear stress plays a critical role in receptor-mediated signalling and has been shown to sensitize cancer cells to apoptosis. Here, Mitchellet al. introduce polymer micro- and nanoparticles tethered to tumour cells to amplify fluid shear stress effects, and find that they can enhance immune cytokine-mediated apoptosis of tumour cells in vitro and in vivo.

Iannacone and colleagues show that the spatiotemporal regulation of type I interferon expression shapes the differentiation of antiviral CD4⁺ T cells into T_FH or T_H1 cells.

A scalable mass cytometry-based method for morphometrically classifying hematopoietic cells demonstrates diagnostic utility when applied to clinical samples.

Testosterone deficiency is associated with autoimmunity and increased B cell numbers, but the underlying mechanism is unclear. Here the authors show that testosterone may modulate the production of B cell survival factor BAFF by fibroblastic reticular cells via regulation of splenic neurotransmitter levels.

Blocking immune checkpoints is a promising strategy to treat lung cancer, but patients often become resistant to the therapy. Here, the authors analyse resistance in mouse models of lung cancer and show in mice and two patients, an increase in the expression of TIM3, which is also involved in the immune response to cancer.

The overexpression of β-catenin and the transcription factor Gata4 in skin fibroblasts induces these cells to secrete reparative exosomes, as shown in mice models of myocardial infarction and Duchenne muscular dystrophy.

This paper demonstrates that a protein complex known as PTEX translocates all malaria parasite proteins destined for export into the cytosol of their host red blood cell.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

The fusion of satellite cells to muscle fibres during adult life is required for both muscle growth and regeneration but it is unknown whether non-muscle cells contribute to this process. Now, Dellavalle and colleagues show that pericytes, cells associated with the vasculature can contribute to both growth and regeneration of muscle fibres.

Cell-cell adhesion of endothelial tissue, mediated by the adhesion molecule VE-cadherin, is tightly regulated. Here the authors show that the F-BAR domain protein pacsin2 is recruited to the trailing end of mechanically unbalanced Focal Adherens Junctions, where it inhibits internalization of VE-cadherin and protects cell-cell adhesion.