Degefu et al. combine highly-multiplexed single-cell measurements with mechanistic modeling and machine learning to show how dimerization-dependent, co-regulated, and competitive AP-1 network interactions generate phenotypic heterogeneity and adaptive transitions underlying melanoma differentiation-state plasticity. The study reveals network-level principles governing AP-1-driven plasticity and a framework to dissect and modulate it.

RNA fingerprinting is a statistical framework that infers causal regulators from single-cell experiments by mapping their transcriptional responses onto reference perturbation dictionaries.

By restoring some functions to intact brains from deceased donors, the startup Bexorg hopes to create a better drug development test bed for neurodegenerative diseases

Viral mimicry is the activation of antiviral immune responses by endogenous nucleic acids that have accumulated in the cytosol. In this Review, Chen et al. highlight how cancer-associated epigenetic and transcriptional dysregulation promotes the generation of immunogenic nucleic acids, which can limit tumour progression. They further outline the mechanisms tumours use to suppress these responses, and the evidence that escape from viral mimicry is central to tumour evolution and a potential target for therapy.

During an immune response, metabolism changes dramatically. Metabolites are oxidized to power immune cell functions, serve as building blocks for proliferation, and act as effectors to regulate pathog...

Gabandé-Rodríguez, Soto-Heredero and colleagues identify an accumulation of cytotoxic CD4+ T cells producing CCL5 in the bone marrow during aging, linked to age-associated myelopoiesis. CCR5 blockade ...

Sprint-interval exercise (SIE) is a time-efficient exercise prescription. However, how short bursts of physical activity promote metabolic health remains unclear. Olsen et al. show that SIE stimulates greater remodeling of plasma, skeletal muscle, and adipose tissue than moderate-intensity exercise, suggesting that predicted interorgan crosstalk may contribute to SIE’s metabolic benefits.

Bocci et al. developed a computational method, scRICH, which leverages single-cell transcriptomics data to quantify cell-cell communication heterogeneity within cell populations. By integrating cell t...

Mitochondrial complex II, succinate dehydrogenase (SDH), links the tricarboxylic acid cycle to the electron transport chain by oxidizing succinate to fumarate and reducing ubiquinone. This unusual position gives Complex II control over bioenergetics, redox state, succinate signaling, and chromatin regulation. In immune cells, Complex II regulates macrophage responses via the succinate–hypoxia-inducible factor-1α–IL-1β axis, T-cell proliferation, lineage commitment, and cytotoxicity. In target tissues of an aberrant immune attack, such as the intestinal epithelium and stem-cell compartments, SDHA loss lowers tissue tolerance, promotes inflammatory memory through succinate-driven epigenetic reprogramming, and amplifies immune-mediated injury. In tumors, SDH loss increases antigen presentation and their susceptibility to T-cell killing. Complex II, therefore, regulates immunopathology through its actions within both attacking immune cells and injured target tissues.

Lipids generated by oxidative stress and their effects on immunity and cancer are reviewed.

Wang et al. demonstrate that TNFAIP8 family proteins play an indispensable role in maintaining neutrophil homeostasis in the steady state, mainly by regulating neutrophil death. TNFAIP8 inhibits the activation of PI3K-AKT signaling to mediate neutrophil survival probably by affecting PIP3 distribution.

Boden et al. define a core transcriptional signature shared across diverse forms of human trained immunity. Their analysis reveals common inflammatory, metabolic, and iron-regulatory programs alongside loss of anti-inflammatory pathways, providing a framework for identifying maladaptive innate immune training and informing the development of diagnostic strategies for inflammation-related pathologies.

Liu et al. integrate spatial transcriptomic, genomic, and proteomic profiling to map colorectal cancer metastases. They reveal early clonal divergence, stem-like features, and immunosuppressive microenvironments with T cell exhaustion in micrometastases, and identify a colorectal liver micrometastasis (CLiMi)-specific six-gene signature associated with MRD status, disease-free survival, and chemotherapy resistance.

Swanton and colleagues provide an overview on intratumor heterogeneity and cancer evolution arising from genetic factors and non-genetic regulation of cancer cells, the tumor microenvironment and the ...

Ye et al. profile primate bone marrow aging across anatomical sites and show that long-term VC supplementation attenuates age-related decline by restoring progranulin-mediated signaling.

Arginine availability regulates arginyl tRNA levels and codon-dependent translation of MHC class I, tuning antigen presentation and shaping anti-viral and anti-tumor immunity.

Nature Metabolism, Published online: 08 July 2026; doi:10.1038/s42255-026-01566-0The HTRA2–CLPB proteostasis system is a mitochondrial quality control module whose dysfunction drives local oxygen toxicity, which can be mitigated by lowering ambient oxygen levels.

Hao et al. develop a non-genetic reprogramming strategy using IFNγ training and Abraxane arming to create meta-neutrophils, which sustain antitumor phenotype and enable potent chemo-immunotherapy against lung metastatic triple-negative breast cancer (TNBC), overcoming cell source limitations.

Ogawa et al. show that oncogenic hepatocytes upregulate FGF21 to suppress early hepatocarcinogenesis. Using single-cell RNA sequencing and Xenium spatial transcriptomics, they reveal that FGF21 induces cell competition by driving migration of surrounding normal cells.

The presence of tertiary lymphoid structures (TLSs) associates with improved anti-tumor immunity, and as such, understanding why some tumors develop TLSs is of prime interest. In the current issue of Cancer Cell, Kirschstein et al. demonstrate that TGFβ-driven programming of myofibroblastic cancer-associated fibroblasts blocks reticular fibroblast differentiation and TLS formation in pancreatic cancer, a barrier reversible by TGFβR1 inhibition.

Nature Reviews Cancer, Published online: 14 May 2026; doi:10.1038/s41568-026-00938-8Colitis predisposes to colorectal cancer, but how inflammation promotes tumour initiation has remained unclear. Nagaraja et al. show that inflammatory injury imprints a heritable epigenetic memory in colonic stem cells that enhances AP-1-driven proliferative programs and accelerates malignant outgrowth following oncogenic mutation.

Summary: The call to arms for alternatives to model organisms of disease will fail without ongoing integration with – and validation against – complex animal models and support from the animal modelli...

In this issue of Cancer Cell, Hayward et al. show that fibrotic tissue tension creates a mechanically organized mutagenic niche. A stiff stroma activates epithelial STAT3, recruits macrophages, and drives NOX-dependent lipid peroxidation, generating diffusible aldehydes that damage epithelial DNA in fibrotic tumors and mammographically dense breast tissue.

An unbiased niche-labeling method, SAMENT, maps cellular and molecular features of metastatic niches and highlights the role of ERα⁺ niche macrophages in preventing T cell infiltration, thereby promoting bone metastasis.

Bub et al. use single-cell RNA sequencing and new macrophage depletion models to discover niche-derived signals that promote monocyte-derived macrophages.

Metastatic breast cancer accounts for 7% of cancer-related deaths, with the lungs being a common site of cancer spread. In parallel, lower respirat...

This Review synthesizes emerging insights into how microenvironmental cues, epigenetic programmes and immune interactions govern disseminated cancer cell dormancy and outlines how advances in dormancy...

Nature Reviews Immunology, Published online: 23 April 2026; doi:10.1038/s41577-026-01291-5What is unique about the immune system of people who live to extreme old age? Here the authors describe that centenarians may achieve such longevity through several mechanisms, including limiting the pathological effects of inflammageing and immunosenescence, preservation of immune surveillance, sustained gut microbial diversity and maintenance of intestinal barrier integrity.

Clonal competition eliminates most early neoplastic lesions, yet a subset persists and ultimately progresses. In Nature, Skrupskelyte et al. demonstrate that nascent tumors survive by actively reshaping a precancerous niche through epithelial-stromal feedback. This ecological gatekeeping mechanism reframes tumor initiation from a process of mutation accumulation to microenvironmental selection and co-evolution.

Nature Reviews Immunology, Published online: 20 April 2026; doi:10.1038/s41577-026-01296-0Monocytes and macrophages adopt modular programmes in response to cancer cells, which can be viewed as an ‘infectious self’ challenge, and cues from the surrounding tissue environment as well as organism-level variables. These pathophysiological programmes offer therapeutic opportunities for cancer immunotherapy.

Iselin et al. explore how the type I IFN response regulates RNA-binding activity using RNA-interactome capture and extend the RIC protocol to assess the role of phosphorylation in this process. Focusing on MATR3, they highlight how this protocol extension, phospho-RIC, can be used to identify PTM-driven regulatory events.