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The ferroptosis suppressor protein FSP1 has a critical role in ferroptosis protection of tumours across multiple in vivo models and is linked to worse prognosis in human lung adenocarcinoma, suggesting its potential as a therapeutic target in lung cancer.

Loss of the tumor suppressor p53 facilitates the malignant progression of colorectal cancer (CRC) following the initial transformation. Here, the authors report that p53 protein degradation triggered by the MYC/URI axis, is an early event essential for tumor initiation in Wnt activation-based CRC models.

In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

Injection of AAV–shRNA below the pial surface of the spinal cord prevents onset or ameliorates progression in a mouse model of ALS, and achieves widespread delivery to the spinal cord and brain motor centers in adult pigs and non-human primates.

Tumour-associated myeloid cells have been linked to patient outcome and treatment response in multiple cancer types. Here, the authors use deconvolution of single cell RNA-sequencing data to identify myeloid populations which are prognostic across cancer types.

As presented at the ESMO Congress 2025, in the single-arm phase 2 IKF/AIO PHERFLOT trial, the perioperative combination of FLOT chemotherapy with anti-PD-1 and anti-HER2 monoclonal antibodies led to a pathological complete response rate of 48.4% in patients with resectable HER2+ esophagogastric adenocarcinoma, meeting the prespecified co-primary endpoint.

Bruton tyrosine kinase (BTK) inhibitors can interrupt the crosstalk between follicular lymphoma FL cells and macrophages thereby inducing downregulation of pro-survival pathways in FL cells. Here this group reports a phase 2 single-arm trial evaluating the regimen of acalabrutinib with lenalidomide plus rituximab on twenty four patients with previously untreated FL.

Interleukin-7 receptor alpha (IL7Ra) is important for lymphoid cell development but its role in leukaemogenesis is not clear. Here, the authors generate a knock-in murine model to show that activating mutations in IL7Ra can initiate precursor B-cell acute lymphoblastic leukaemia.

Glutamate metabolically reprograms bone-marrow-derived macrophages, stabilizing HIF1α, which transcriptionally activates WNT3 to promote YAP1-dependent hepatocyte proliferation, boosting liver regeneration.

ONECUT2 is a targetable transcription factor that antagonizes androgen receptor signaling and drives androgen independence and neuroendocrine differentiation in castration-resistant prostate cancer.

Resident memory T cells (Trm) are memory T cells that remain in tissue. Here, the authors show that induction of Trm cells is required for control of tumour growth following mucosal vaccination in mice bearing head and neck cancer and that Trm cells in human lung cancer correlates with a better survival.

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.

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.

Clapes et al. show that chemotherapy leads to chromatin reorganization and increased expression of transposable elements, which promote an MDA5-driven inflammatory response that enhances haematopoietic regeneration.

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.

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.

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.

Stathmin-2 is lost in amyotrophic lateral sclerosis. Here the authors show that stathmin-2 has an essential role in the maintenance of axon structure, with its loss from adult motor neurons resulting in axonal collapse and muscle denervation.

Quezada and colleagues develop improved anti-CD25 antibodies that preserve IL-2 signaling and enhance single-agent antitumor immunity and immunotherapy through specific and efficient T_reg cell depletion.

High salt intake changed the gut microbiome and increased T_H17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T_H17 cells and increased blood pressure in humans.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

Proteins SBP1 and MAHRP1 of the human malaria parasite are required for sequestration of infected red blood cells in major organs. Here, De Niz et al. identify homologous proteins in the rodent parasite Plasmodium berghei, showing that they play similar roles and supporting the usefulness of malaria mouse models.

Many cancer immune therapy approaches depend on an HLA-restricted neoantigen-specific T cell response. AUs show here that Zoledronic acid can expand, and induce tumour recognition by, a population of tissue resident memory gamma-delta T cells associated with an efficient anti-tumour immune response in hepatocellular carcinoma.

In response to some signals, dendritic cells can become tolerogenic. Rabinovich and colleagues show that galectin-1 drives the differentiation of tolerogenic DCs via a circuit involving interleukins 27 and 10.

When monkeys are infected with a virus similar to HIV, treated with antiretroviral therapy (ART), and are administered a ‘combo therapy’ made of antibodies against molecules that inhibit immune responses, they control viral rebound when ART is discontinued for more than 6 months

Lupus-like disease is driven by NETs enriched in mitochondrial DNA.

Dysregulation of an mTORC1 substrate-specific mechanism leads to constitutive activation of TFEB, and promotes kidney cystogenesis and tumorigenesis in a mouse model of Birt–Hogg–Dubé syndrome.

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.

Neutrophils are crucial regulators of the innate immune response and act as a first line of defence against invading microorganisms. To target microorganisms, neutrophils release extracellular structures called neutrophil extracellular traps (NETs), which externalize key autoantigens. In this Review, Gupta and Kaplan explore the contribution of neutrophils and NETs to the pathophysiology of systemic autoimmune disorders that can affect the kidneys, and discuss neutrophils as novel therapeutic targets for these diseases.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

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.

A multi-ancestry genome-wide association study meta-analysis, combined with transcriptome- and methylome-wide association analyses, identifies risk loci associated with colorectal cancer. Credible effector genes and their target tissues are also highlighted, showing that over a third probably act outside the colonic mucosa.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

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

Park et al. show that in the process of metastasis, dying tumor cells enhance the outgrowth of their surviving counterparts via nuclear expulsion, resulting in an extracellular DNA–protein complex that activates RAGE receptors on tumor cells.

Here the authors identify GPATCH11 variants responsible for retinal dystrophy with neurological impairment and facial dysmorphy. They explore its function using a mouse model and demonstrate GPATCH11’s involvement in RNA regulation and splicing.

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.

Here, Pala et al. show that mosquito salivary apyrase regulates hemostasis in the mosquito blood meal, boosting malaria transmission. They demonstrate that immunizing against apyrase inhibits parasite transmission.

The biological understanding of poor prognosis associated with lymph node metastasis in head and neck cancer (HNC) remains crucial. Here, a proteomic characterisation of 140 multisite samples from a 59-HNC patient cohort and machine learning reveals potential biomarkers and metastasis related signatures.