FDA approves vepdegestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer

The concept of PANoptosis describes the simultaneous activation of pyroptosis, apoptosis and necroptosis. This Comment discusses the evidence supporting this hypothesis and proposes criteria to valida...

mRNA–lipid-nanoparticle vaccines do not require type 1 conventional dendritic (cDC1) cells or the WDFY4-dependent cross-presentation pathway for CD8+ T cell priming but, instead, engage both cDC1 and ...

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship be...

Upstream open reading frames exert translational control of TNFR1, which limits tissue responsiveness to TNF.

The non-canonical inflammasome, comprising caspase-4 in humans, initiates pyroptosis upon sensing cytosolic lipopolysaccharide (LPS) from Gram-negativ…

Hanahan revisits the evolving framework of cancer hallmarks, synthesizing 25 years of conceptual refinement into a multidimensional view of tumor biology. This review highlights how aberrant capabilities, enabling traits, microenvironmental players, and systemic interactions converge to drive tumorigenesis and proposes that mechanism-guided co-targeting of hallmarks may offer promising therapeutic strategies.

In a mouse model, environmental immunostimulation in early life led to cross-reactive adaptive immune memory and reduced type II immune responses to allergens, indicating a mechanistic relationship be...

Type III interferons are essential immune mediators playing pleiotropic roles during health and disease. In this review, we highlight the molecular and cellular pathways that lead to the production of...

Rizzotto et al. discuss the causes and consequences of deregulated mitosis that allow cells arrested in mitosis to escape to the next interphase, where they can initiate inflammatory signalling or und...

Lymphotoxin alpha represses acute myeloid leukemia by depleting TRAF2 and triggering cell death and myeloid differentiation.

Efficient DNA repair might make possible the longevity of naked mole-rats. However, whether they have distinctive mechanisms to optimize functions of DNA repair suppressors is unclear. We find that na...

Koerner et al. show that RIPK1 autophosphorylation at S161 is crucial for regulating cell death and inflammation. S161N mutation reduces RIPK1 kinase activ

LUBAC preserves adipose tissue integrity via cell death inhibition, preventing metabolic disorders during aging and obesity.

Rapid extracellular antibody profiling reveals a contribution of autoantibodies to the effectiveness of checkpoint immunotherapy for cancer.

Mammalian caspases are a group of cysteine proteases historically categorized into an ‘inflammatory’ subgroup and an ‘apoptotic’ subgroup, although accumulating evidence indicates that this distinctio...

Hegazy and colleagues demonstrate that epithelial oncostatin M receptor expression drives gut inflammation and tumor formation.

VDAC2 deficiency elicits uncontrolled IFNγ-induced BAK activation and mitochondrial damage for improved cancer therapy.

Immune checkpoint blockade activates T cell immunity by reprogramming the STAT3 and STAT5 transcriptional pathways in dendritic cells, and STAT3 degradation is effective for treating tumours...

Nature - Molecular basis of SIFI activity in the integrated stress response

MPO activates an immunometabolic rheostat to restrict the functional plasticity of macrophages in favor of proresolving properties.

Cembellin-Prieto and colleagues find that B cells in the lung are capable of producing acetylcholine and that these regulate early macrophage activation and control influenza virus replication.

Song et al. demonstrated that the cytosolic CYCS-INPP4A complex inhibits ferroptosis by promoting phosphatidylinositol-3-phosphate synthesis and preventing phospholipid peroxidation. The small molecule 10A3 disrupts this complex, enhancing ferroptosis-mediated tumor suppression and offering a therapeutic strategy.

Nature Reviews Genetics, Published online: 14 April 2025; doi:10.1038/s41576-025-00830-5ADAR1-mediating RNA editing enables the cell to distinguish between endogenous and viral RNA. Li and Walkley review findings from human and mouse genetics that have revealed the mechanisms of ADAR1-mediated RNA editing, which are now providing insights for the development of potential therapies that target these mechanisms.

Necroptosis is an inflammatory form of regulated cell death implicated in a range of human pathologies, whose execution depends on the poorly understo…

The incidence of prostate cancer is increasing. Screening with an assay of prostate-specific antigen (PSA) has a high rate for false positive results. Genomewide association studies have identified...

In an iterative phase 2 trial, patients with metastatic, treatment-refractory, mismatch repair proficient gastrointestinal cancers had responses to neoantigen-reactive tumor-infiltrating lymphocytes b...

Skin injury releases damage-encoded systemic signals that can initiate immunity to novel antigens introduced at distal barrier sites.

Cheng et al. identify a mitochondrial complex IV (CIV) deficiency in the brains of patients with sporadic amyotrophic lateral sclerosis (ALS). They demonstrate that defects in mitochondrial CIV induce...

TBK1 and IKKe prevent premature cell death by limiting the activity of multiple death pathways in myeloid cells.

ZBP1 and mitochondrial Z-DNA drive autoimmune photosensitivity via cGAS-STING activation.

Inhibition of cyclooxygenase 1 releases T cells from immunosuppression by platelet-derived thromboxane A2, thereby enhancing the immune response against metastasis.

The involvement of cell death pathways in the early stage of pancreatic ductal adenocarcinoma (PDAC) development, especially KRAS-dependent acinar-to-ductal metaplasia (ADM), remains to be investigated. Here, the authors find that TAK1 mediates cell survival during ADM transdifferentiation through suppression of apoptosis and necroptosis, which could be targeted for prevention and treatment of PDAC.

ZBP1 is known to initiate RIPK3-mediated necroptosis in murine models of viral infection, but how this pathway is regulated in human cells is unclear. This study shows that, unlike in the mouse, RIPK1...

In a phase 1 trial, patients with pancreatic ductal adenocarcinoma who were treated with surgery and bespoke neoantigen mRNA vaccines combined with anti-PD-L1 and chemotherapy exhibited marked lo...

The cGAS-STING pathway induces autophagy to deliver cytoplasmic DNA and invading pathogens to lysosomes for elimination. However, whether lysosome function is regulated by the cGAS-STING pathway remai...

Acha-Sagredo et al. stratify colorectal cancers using features of an immune-reactive tumor microenvironment. This microenvironment, locally abundant in cytotoxic lymphocytes and antigen-presenting mac...

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patie...