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Glioblastoma—the deadliest form of brain cancer—alters the calvarial bone and its marrow components, pushing it toward producing more myeloid cells and contributing to an immunosuppressive environment.

The authors present a molecular classification of acute leukemia using 5-methylcytosine signatures, together with a neural network-based classifier for clinical use.

DiNardo et al. perform a phase 1b/2 clinical trial of telaglenastat (CB-839) in combination with azacytidine in persons with advanced myelodysplastic syndromes and report on the treatment safety and efficacy, including a definition of clinical responders.

Current multiomics integration methods frequently suffer from limitations in transparency, modularity, deployability, and broad applicability. Here, the authors develop Flexynesis, a framework for multiomics integration that allows users to choose from multiple options and model architectures; it can be used for multiple tasks and pipelines, with applications in precision oncology.

The immune receptor Transmembrane and immunoglobulin domain containing 2 (TMIGD2) mediates T-cell and nature killer cells co-stimulation upon B7-family HHLA2 engagement. Here, the authors show that TMIGD2 is expressed in Acute Myeloid Leukaemia stem cells regulating self-renewal and differentiation to facilitate leukemogenesis.

Breast cancer cells interact with neighbouring adipocytes, but the mechanisms are not fully understood. Here, the authors show that triple-negative breast cancer (TNBC) cells transfer cAMP through gap junctions, activating lipolysis in tumour-associated adipocytes to promote TNBC growth.

In a large cohort of patients who underwent non-cardiac surgery, postoperative prescription of oral anticoagulation medication decreased the risk of stroke in patients with postoperative atrial fibrillation (POAF), especially for patients deemed to be at high risk for POAF based on a newly developed risk score.

The intestinal stroma secretes WNT ligands but the role of WNT in intestinal repair is unclear. Here, the authors show that when WNT synthesis is ablated from stromal macrophages, the intestine morphology is normal but hypersensitive to radiation injury, implicating macrophage-derived WNT in intestinal repair.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

Pinho et al. show that VCAM1 and MHC-I cooperate to provide a ‘don’t-eat-me’ signal that prevents haematopoietic stem cells clearance by mononuclear phagocytes, and also that VCAM1 can be hijacked by cancer cells to escape innate immune surveillance.

Several vaccines have been approved for Covid-19 and effectiveness data could guide public health decisions on vaccine usage. Here, the authors compare effectiveness of BNT162b2 and ChAdOx1 vaccines in people over 50 in the UK and find that BNT162b2 confers lower risk of infection and hospitalization.

Total cell cycle duration is a key hallmark of cancer initiation, and determines whether defects in apoptosis, senescence, immune surveillance, angiogenesis, DNA repair, polarity and proliferation lead to cancer development.

HistoPlexer, a deep learning model, generates multiplexed protein expression maps from H&E images, capturing tumour–immune cell interactions. It outperforms baselines, enhances immune subtyping and survival prediction and offers a cost-effective tool for precision oncology.

17β-oestradiol establishes an anti-ferroptotic state in female kidney tubules.

Opioid-induced respiratory depression can be treated with intranasal (IN) or intramuscular (IM) naloxone. Here the authors report a randomized, crossover, open-label trial showing that lower number of IM doses are required for full reversal of breathing following fentanyl-induced apnea by comparison to IN doses.

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.

Understanding of the genetic factors and molecular mechanisms underlying neurodevelopmental disorders remains incomplete. In this study, authors show that microdeletions in the gene ANKS1B lead to loss of the neuronal synapse-enriched protein AIDA-1 and to a novel neurodevelopmental syndrome

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

The molecular landscape of chromothriptic medulloblastoma remains to be characterised. Here, spatial transcriptomics analysis of 13 chromothriptic and non-chromothriptic medulloblastomas identifies distinct spatial composition patterns and cell communication networks in these tumours.

Minimal reduction of PU.1 in mice is sufficient to elicit a preleukemic state that, when combined with a DNA mismatch repair defect, results in progression to myelodysplastic syndrome and acute myeloid leukemia.

The hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate antitumour innate immune responses via endoplasmic reticulum stress in antigen-presenting cells.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, the authors use phosphoproteomics to define kinases with distinct activity profiles in TNBC, demonstrating their prognostic value as well as their utility for simplifying TNBC classification and designing drug regimens.

Cui et al. identify an important role for MLL3 in regulating the hybrid epithelial–mesenchymal transition state in breast cancer and show that deletion of MLL3 enhances metastatic capacity through increased IFNγ signalling.

Mutations in mitochondrial genes cause untreatable diseases such as Leigh syndrome (LS). Here, authors show that cannabidiol (CBD) administration can extend lifespan and improves pathology in LS mouse models, mediated by PPARγ.

In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

Here, Burk et al. develop an algorithm to diagnose bacterial vaginosis (BV) using the 16S rRNA gene, called molBV, which they use to profile the inflammatory landscape of BV and predict progression of human papillomavirus infection to cervical pre-cancer.

During myocardial infarction, cardiac macrophages expand, become activated and play an important role in cardiac repair and remodelling. Here the authors show that integrin α5 is upregulated in infarct macrophages and contributes to myocardial repair, triggering an angiogenic phenotype and protecting from adverse remodelling.

Myelomagenesis progresses through well-defined pre-malignant states. Here, using single-cell RNA sequencing and T cell receptor repertoire analysis of bone marrow T cells in patients at different stages of myelomagenesis, the authors identify large clonotypic expansions characterized by the expression of multiple immune checkpoints.

The transcription factors ZEB1 and YAP function in different pathways yet both activate aggressive behaviour in cancer cells. Here, the authors describe that the proteins physically interact and that this changes the transcriptional activity of ZEB1 from a repressor to an activator.

In a phase 2 trial of patients with untreated, recurrent and progressive brain metastases treated with an anti-programmed cell death protein 1 inhibitor, the overall intracranial benefit rate was 42.1%, which met the prespecified primary endpoint.

Analysis of exomes and transcriptomes from 100 African American patients with acute myeloid leukemia identifies ancestry-related variation in mutation profiles and survival. Refined risk classification suggests clinical relevance of these ancestry-associated differences.

Liang Zhu and colleagues report that inactivation of Skp2, a target of the pRb tumor suppressor, completely prevented tumorigenesis in tumor-prone mice with loss of one Rb1 allele. This work nominates Skp2 as a drug target to combat Rb1-deficient tumors.

Barnett et al. explore the role of blood-based tumor mutation burden in predicting outcomes to immune checkpoint inhibitors in patients with advanced breast or prostate cancers. They find immune checkpoint inhibitors were not offered based on blood-based tumor mutation burden, and this did not predict response.

Polycomb Repressor Complex 2 (PRC2) is frequently up-regulated in cancers. Here, the authors show that the tyrosine kinase c-Src stimulates mitochondrial function to signal energy sufficiency to mTORC1, increasing translation of the PRC2 subunits EZH2 and SUZ12 to support ErbB2-dependent tumours.

High-grade meningiomas have a poor prognosis with virtually no effective systemic therapies. Here, the authors report results of a phase 2 clinical trial demonstrating safety and activity of pembrolizumab, a PD-1 inhibitor, in patients with recurrent and residual high-grade meningiomas.

In a phase 1 trial of patients with advanced systemic mastocytosis, avapritinib, a selective KIT inhibitor, was generally well tolerated, elicited durable clinical responses and led to reductions in mast cell disease burden.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.