Cell Reports Medicine

Nonsense-mediated mRNA decay inhibits TRAF6-dependent anti-tumor immunity in colorectal cancer Wang et al. demonstrate that nonsense-mediated mRNA decay (NMD) is abnormally activated in CRC. Inhibiting NMD remodels the tumor microenvironment by activating the TRAF6-TBK1 axis and boosting CD8+ T cell function—ultimately improving the efficacy of ICB therapy, offering a clinically actionable strategy to improve CRC immunotherapy outcomes.

Online now: Nonsense-mediated mRNA decay inhibits TRAF6-dependent anti-tumor immunity in colorectal cancer

Ngn2 and Isl1-mediated astrocyte-to-neuron conversion in vivo promotes functional recovery after spinal cord injury Zhou et al. show that activation of Ngn2 and Isl1 enabled reactive astrocytes to convert into neurons, which promotes functional recovery after spinal cord injury, with new neurons forming synaptic connections with ascending and descending neural pathways, and promoted propriospinal axon regeneration and improved the neuromuscular junction morphology and function of muscle.

Online now: Ngn2 and Isl1-mediated astrocyte-to-neuron conversion in vivo promotes functional recovery after spinal cord injury

Precision prediction of venetoclax-azacitidine treatment efficacy in acute myeloid leukemia via integrative drug screening and machine learning Jin et al. integrate drug sensitivity testing, transcriptomics, and functional assays to uncover key determinants of venetoclax-azacitidine (VEN/AZA) response in AML. They develop an eight-gene model (RF8) that links drug response with mutations and survival, offering a precision medicine framework to guide VEN/AZA therapy beyond conventional genetic markers.

Online now: Precision prediction of venetoclax-azacitidine treatment efficacy in acute myeloid leukemia via integrative drug screening and machine learning

Unlocking the tumor microenvironment: Innovative strategies for cancer therapy and translational insights The tumor microenvironment (TME) is a highly complex and dynamic ecosystem composed of diverse cellular and extracellular components that critically influence cancer initiation, progression, and resistance to therapy. Over the past few decades, extensive research has elucidated the interactions between tumor cells, the surrounding stroma, and the immune system, underscoring the TME’s pivotal role in oncogenesis and responses to therapy.

Online now: Unlocking the tumor microenvironment: Innovative strategies for cancer therapy and translational insights

Online now: Voices: Future directions in targeting the tumor microenvironment

Online now: Q&A with Karin de Visser

From bench to body: In vivo CAR engineering in the clinic In vivo CAR engineering is an emerging therapeutic platform for cancer and autoimmune diseases. Enabled by advanced delivery systems such as immune-evasive lentiviral vectors and targeted lipid nanoparticles, this strategy has progressed to early clinical testing, showing initial safety and efficacy. Here, key opportunities and translational hurdles are critically discussed.

Online now: From bench to body: In vivo CAR engineering in the clinic

From visualization to prediction: Dissecting metabolic heterogeneity with DDRTree The discriminative dimensionality reduction tree (DDRTree) framework provides a powerful approach to unravel metabolic heterogeneity and delineate clinically relevant subtypes. In this issue, Qiu et al. and Jia et al. apply it to type 2 diabetes and obesity, identifying subtypes with distinct risk profiles.

Online now: From visualization to prediction: Dissecting metabolic heterogeneity with DDRTree

System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells Everolimus is approved for treating advanced ER+ breast cancers, yet many patients develop resistance. Medina et al. identify SMARCD3 regulons linked to activation of alternate growth-factor signaling and MEK1/2 inhibitor sensitivity in resistant cells, revealing an effective strategy to overcome everolimus resistance in ER+ breast cancer.

Online now: System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells

A prognostic index integrating deep learning baseline PET/CT biomarkers and multi-omics profiling in diffuse large B cell lymphoma Wang et al. develop a clinical-imaging-multi-omics prognostic index for diffuse large B cell lymphoma by integrating quantitative PET/CT biomarkers, genetic subtypes, and clinical risk factors. By analyzing large cohorts of patients, key biomarkers—total metabolic tumor volume and lactate dehydrogenase—that reflect immunosuppressive microenvironments and tumor proliferation were identified.

Online now: A prognostic index integrating deep learning baseline PET/CT biomarkers and multi-omics profiling in diffuse large B cell lymphoma

Taking programmed cell death from mechanisms to interventions

Together with our partners at Zhejiang University, Liangzhu Laboratory, we're thrilled to announce the Cell Symposium: Taking programmed cell death from mechanisms to interventions, taking place in Hangzhou, China, October 22–24, 2026
http://dlvr.it/TPMsG2
#CSCellDeath26

Virus envelope glycoprotein targeting bispecific T cell engager protects mice from lethal severe fever with thrombocytopenia virus infection Peng et al. reveal that the impaired cytotoxicity and exhausted state of T cells are significantly associated with lethal outcomes in SFTS patients and demonstrate that Gn-targeted bispecific T cell engager antibodies significantly protect mice against lethal SFTSV infection by redirecting T cells to kill infected cells.

Online now: Virus envelope glycoprotein targeting bispecific T cell engager protects mice from lethal severe fever with thrombocytopenia virus infection

A gardener removes weeds among flowers—just like therapies targeting the tumour microenvironment can eliminate cancer cells while sparing healthy ones. Dive into our special issue for expert reviews on immune cell targeting in cancer! Artwork by Justine Reimand. www.cell.com/issue/S2666-...

Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy offspring Zhao et al. translationally demonstrate how maternal diabetes induces early-onset endothelial dysfunction in sons, but not daughters, even when offspring are metabolically healthy. This challenges prior findings that metabolic dysfunction is the primary driver of cardiovascular disease in this population, guiding future clinical practice and risk management of these individuals.

Online now: Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy offspring

A combined genomic arrhythmia propensity score delineates cumulative risk Monroe et al. analyze genome sequencing from individuals with early-onset ventricular arrhythmias. Combining the effect of common genetic variants with rare coding and noncoding regulatory variants in cardiomyopathy and arrhythmia genes predicts outcomes. Each component additively predicts arrhythmia with the cumulative GAPS performing best.

Online now: A combined genomic arrhythmia propensity score delineates cumulative risk

Plasma proteomics identifies proteins and pathways associated with incident epilepsy Zhang et al. utilize large-scale plasma proteomic data to investigate the association between 2,920 plasma proteins and the risk of incident epilepsy. They characterize the temporal trajectories of epilepsy-associated protein levels preceding disease onset and perform clustering analysis. Ultimately, they develop a protein-based predictive model for assessing future epilepsy risk.

Online now: Plasma proteomics identifies proteins and pathways associated with incident epilepsy

Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche In this review, Aprile et al. highlight the clinical application of gene therapy by gene addition and gene editing, and the novel findings about hematopoietic stem cell and bone marrow niche features and function in beta-thalassemia and sickle cell disease.

Online now: Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche

A combined genomic arrhythmia propensity score delineates cumulative risk Monroe et al. analyze genome sequencing from individuals with early-onset ventricular arrhythmias. Combining the effect of common genetic variants with rare coding and noncoding regulatory variants in cardiomyopathy and arrhythmia genes predicts outcomes. Each component additively predicts arrhythmia with the cumulative GAPS performing best.

Online now: A combined genomic arrhythmia propensity score delineates cumulative risk

Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy offspring Zhao et al. translationally demonstrate how maternal diabetes induces early-onset endothelial dysfunction in sons, but not daughters, even when offspring are metabolically healthy. This challenges prior findings that metabolic dysfunction is the primary driver of cardiovascular disease in this population, guiding future clinical practice and risk management of these individuals.

Online now: Maternal diabetes programs sexually dimorphic early-onset cardiovascular dysfunction in metabolically healthy offspring

The tumor microenvironment of 14,837 breast cancers is associated with clinical outcome independently of genomic subtypes Tu et al. present a systematic analysis of the tumor microenvironment across 14,837 breast cancers, identifying distinct cellular patterns that predict disease-specific survival independently of genomic and intrinsic subtypes. Characterizing microenvironment composition may provide critical prognostic markers that can complement current molecular classification for treatment selection and preventing recurrence.

Online now: The tumor microenvironment of 14,837 breast cancers is associated with clinical outcome independently of genomic subtypes

Glucocorticoid-induced changes of the gut microbiota and metabolic markers in healthy young men: Outcome of a randomized controlled trial Lyu et al. show that short term oral or intramuscular glucocorticoid interventions trigger a gut dysbiosis in randomized controlled trials of healthy men. The dysbiosis shows both administration-route specific and shared features. The authors identify specific bacterial species with abundance that associate with measures of host metabolism.

Online now: Glucocorticoid-induced changes of the gut microbiota and metabolic markers in healthy young men: Outcome of a randomized controlled trial

Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research (Cell Reports Medicine 5, 101350; January 16, 2024)

Online now: Microbiome preterm birth DREAM challenge: Crowdsourcing machine learning approaches to advance preterm birth research

Non-orthosteric inhibition of enolase 1 impedes growth of triple-negative breast cancer Tailor et al. identify enolase 1 (ENO1) as the target of SU212, a promising therapeutic candidate for triple-negative breast cancer (TNBC). By inducing ENO1 degradation, SU212 reduces tumor growth with minimal toxicity, maintains efficacy in diabetic models, and shows favorable pharmacology, underscoring its strong potential for clinical translation.

Online now: Non-orthosteric inhibition of enolase 1 impedes growth of triple-negative breast cancer

Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS Shahbaz et al. find that female long COVID patients with ME/CFS exhibit heightened inflammation, altered hematopoiesis, disrupted hormone levels, and neuroinflammatory gene signatures. In parallel, our study identifies sex-specific immune and hormonal biomarkers that correlate with clinical symptoms, supporting the need for tailored therapeutic strategies, including consideration of hormone replacement therapy.

Online now: Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME/CFS

Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy Chiu et al. show that prolonged cetuximab treatment in head and neck cancer triggers STAT1 Lys637 acetylation, disrupts interferon (IFN)-γ signaling, and drives resistance to immune checkpoint blockade. This identifies a clinically relevant biomarker that links prior therapy to immunotherapy response and suggests strategies for treatment stratification.

Online now: Therapeutic stress triggers tumor STAT1 acetylation to disarm immunotherapy

Aqueous humor biomarkers in ocular oncology: Insights and advances Recent advances in aqueous humor-derived oncologic biomarkers have opened the door to using liquid biopsy to detect and monitor ocular cancers. This review by Cheslow et al. details relevant and notable developments in aqueous humor biomarkers across three of the most common ocular malignancies: uveal melanoma, intraocular lymphoma, and retinoblastoma.

Online now: Aqueous humor biomarkers in ocular oncology: Insights and advances

Developing a therapeutic elastase that stimulates anti-tumor immunity by selectively killing cancer cells Gujar et al. develop N17350, a next-generation therapeutic elastase that selectively kills cancer cells, drives tumor regression, and induces systemic anti-tumor immunity. It remains effective with repeated dosing and in resistant cancers, positioning N17350 as a strong candidate for first-in-human clinical evaluation.

Online now: Developing a therapeutic elastase that stimulates anti-tumor immunity by selectively killing cancer cells

Fluorinated prodrug-engineered nano-remodeler relieves tumor hypoxia for dual-enhanced ferroptosis-immunotherapy Lei et al. design a nano-remodeler composed of a fluorinated JQ1 prodrug and sorafenib to enhance ferroptosis induction and immune activation by reversing the hypoxic and immunosuppressive tumor microenvironment. This synergistic approach effectively counteracts tumor immune escape and demonstrates potent antitumor efficacy through combined ferroptosis and immunotherapy.

Online now: Fluorinated prodrug-engineered nano-remodeler relieves tumor hypoxia for dual-enhanced ferroptosis-immunotherapy

Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids Kawamura et al. model antithymocyte globulin (ATG)-induced microvasculopathy in vivo using human iPSC-derived vascularized liver organoids with intravital imaging. ATG provokes a human LSEC-specific, complement-dependent proinflammatory program exacerbated by TGF-β pathway activation. The platform reveals TGF-β signaling as a modifiable contributor to ATG-induced hepatic vascular injury.

Online now: Modeling antithymocyte globulin-induced microvasculopathy using human iPSC-derived vascularized liver organoids

Trilaciclib triggers a neutrophil-related immune response and sensitizes non-small cell lung cancer to anti-PD-1 therapy Trilaciclib promotes antitumor immunity in NSCLC by triggering cGAS/STING-dependent senescence and SASP, leading to increased infiltration and activation of CD177+ neutrophils and CD8+ T cells. Their crosstalk establishes an immunostimulatory feedback loop, supporting combination therapy with anti-PD-1 antibodies.

Online now: Trilaciclib triggers a neutrophil-related immune response and sensitizes non-small cell lung cancer to anti-PD-1 therapy