Cell Reports Medicine

Plasma GDF15 increases during hyperinsulinemic hypoglycemia in humans with post-bariatric hypoglycemia and after insulin exposure in mice Ferraz-Bannitz et al. demonstrate that GDF15 is elevated in individuals with PBH during mixed meal and hyperinsulinemic hypoglycemia, strongly correlating with hypoglycemia symptoms. In mice, hypoglycemia increases GDF15 and rGDF15 blunts food intake responses to hypoglycemia, implicating GDF15 as a conserved counterregulatory response to hypoglycemia in both PBH individuals and mice.

Online now: Plasma GDF15 increases during hyperinsulinemic hypoglycemia in humans with post-bariatric hypoglycemia and after insulin exposure in mice

An integrative multi-omics approach identifies microbiome alterations linked to pathological and behavioral features in autism spectrum disorder Mi et al. integrate gut microbiome, neuroimaging, and plasma metabolome data to characterize the gut-brain axis in ASD. They demonstrate that microbial features are superior predictors of symptom severity and construct a second-order mediation model linking microbes, metabolites, and brain structures to behavior, revealing potential biological pathways involved in ASD.

Online now: An integrative multi-omics approach identifies microbiome alterations linked to pathological and behavioral features in autism spectrum disorder

Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery Li et al. integrate liver function data from Oropouche virus (OROV)-infected patients with human liver-derived organoids to demonstrate hepatic infection and resulting cellular injury. Using organoids, they further show that molnupiravir exerts strong antiviral activity against OROV and synergizes with interferon-alpha.

Online now: Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery

TRPM3 mediates spontaneous pain and mechanical allodynia in a mouse model of chronic orofacial neuropathy Deseure et al. demonstrate that the cation channel TRPM3 is essential for the development of spontaneous pain or mechanical hypersensitivity in a mouse model of chronic trigeminal neuropathic pain. Their findings indicate that pharmacological TRPM3 inhibition may represent a therapeutic target to treat trigeminal neuralgia and related neuropathies in patients.

Online now: TRPM3 mediates spontaneous pain and mechanical allodynia in a mouse model of chronic orofacial neuropathy

Proteogenomic characterization delineates clinically relevant subtypes of advanced differentiated thyroid cancer Zhang et al. systematically reveal the heterogeneity of advanced differentiated thyroid cancer (DTC) from a biological perspective and develop a genomics-pathomics model that provides a preliminary basis for a therapeutic framework to advance precision oncology in this disease.

Online now: Proteogenomic characterization delineates clinically relevant subtypes of advanced differentiated thyroid cancer

Integrative CSF profiling identifies disease-specific immune responses in leptomeningeal disease Nieto et al. profile cerebrospinal fluid cells in leptomeningeal disease across tumor entities and compare them with blood and tissue lesions using single-cell and spatial approaches, showing that the CSF is an immune-active compartment reflecting immune responses holding the potential to capture treatment resistance and tumor progression.

Online now: Integrative CSF profiling identifies disease-specific immune responses in leptomeningeal disease

Molecular taxonomy of pancreatic neuroendocrine tumors reveals BEND2-fusions-driven transcriptional plasticity and therapeutic vulnerabilities Lu et al. identify BEND2 fusions in ∼5% of pancreatic neuroendocrine tumors, defining an aggressive Gastrin-high subtype. Integrating bulk and single-nucleus RNA sequencing with functional assays, BEND2 fusions are shown to drive transcriptional plasticity and nominate chromatin and immune signaling programs as actionable therapeutic targets.

Online now: Molecular taxonomy of pancreatic neuroendocrine tumors reveals BEND2-fusions-driven transcriptional plasticity and therapeutic vulnerabilities

Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression Liu et al. delineate ESCC molecular and cellular dynamics via spatial profiling of 32 tumors. Sustained activation of key pathways such as PI3K/AKT and dynamic immune microenvironment remodeling are identified during ESCC evolution. Functional assays confirm that OGT, upregulated in late-stage ESCC, drives tumor invasive potential.

Online now: Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression

Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights Hoel et al. characterize circulating proteomic signatures in ME/CFS and identify widespread tissue-linked alterations, including increased secreted proteins and reduced intracellular proteins. Protein changes affecting immune, metabolic, and vascular processes support immune reprogramming and define regulatory networks that provide pathobiological insight relevant to biomarker development and future therapeutic strategies.

Online now: Charting the circulating proteome in ME/CFS using cross-system profiling to uncover mechanistic insights

Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy Sun et al. establish a PDX-linked osteosarcoma organoid biobank and rebuild immune infiltration by co-culturing organoids with human PBMCs. This platform connects tumor genotype and immune context to therapeutic response, enabling ex vivo drug testing and supporting a precision combination strategy for Chr9p21.3/MTAP-deleted osteosarcoma.

Online now: Reconstruction of T cell infiltration in an osteosarcoma PDX-organoid interactive biobank for personalized immunotherapy

A strategy of microglia replacement alleviates microgliopathy in a CSF1R I794T hotspot mutation mouse model of CSF1R-related disorder Li et al. define the clinical features of patients carrying the CSF1R p.I794T variant and establish a corresponding knockin mouse model. They show that Csf1rI792T/+ microglia adopt a disease-associated state and that a microglial replacement strategy, DCMDT, mitigates cognitive and neuropathological deficits in CSF1R-related disorder.

Online now: A strategy of microglia replacement alleviates microgliopathy in a CSF1R I794T hotspot mutation mouse model of CSF1R-related disorder

Therapeutic base editing alleviates restrictive cardiomyopathy Chang et al. establish a faithful mouse model of Tnni3-mutant restrictive cardiomyopathy. They demonstrate that in vivo adenine base editing corrects the genetic defect, reversing diastolic dysfunction and preventing premature mortality. This study highlights the therapeutic potential of base editing for severe genetic heart diseases.

Online now: Therapeutic base editing alleviates restrictive cardiomyopathy

Valrubicin-loaded immunoliposomes targeting antigens on immunosuppressive cells to circumvent resistance to cancer immunotherapy Georgievski et al. report valrubicin-loaded immunoliposomes (Val-ILs) that target immunosuppressive cells in mouse cancer models. These Val-ILs affect the expression of nine antigens expressed by pro-tumor immunosuppressive cells, reprogram tumor-associated macrophages, increase tumor-infiltrating lymphocytes into the tumor microenvironment, and enhance anti-PD-1 efficacy. In murine models of both responsive and resistant cancers, this strategy restores anti-tumor immunity, improves tumor control, and limits metastasis.

Online now: Valrubicin-loaded immunoliposomes targeting antigens on immunosuppressive cells to circumvent resistance to cancer immunotherapy

Neoadjuvant Fc-enhanced anti-CTLA-4 targets Tregs to augment androgen deprivation in high-risk prostate cancer: A randomized phase I trial Ager et al. investigate immunological effects of a next-generation Fc-enhanced αCTLA-4 antibody with hormonal therapy in a phase I neoadjuvant clinical trial in high-risk localized prostate cancer, leveraging single-cell multi-omics approaches. Their findings establish clinical feasibility, effects of Fc-enhanced αCTLA-4 on regulatory T cells, and putative response biomarkers.

Online now: Neoadjuvant Fc-enhanced anti-CTLA-4 targets Tregs to augment androgen deprivation in high-risk prostate cancer: A randomized phase I trial

Phylogenomics-driven metalloantibiotic engineering: Overcoming ciprofloxacin resistance in Pseudomonas aeruginosa with sideromycin-bismuth synergy Chen et al. report a phylogenomics-guided strategy to devise a sideromycin-bismuth metalloantibiotic that overcomes ciprofloxacin resistance in P. aeruginosa. The self-assembled complex enters bacteria via iron uptake pathways and exerts three-pronged lethality by disrupting DNA integrity, ATP production, and potassium transport, demonstrating potent in vivo efficacy with favorable safety.

Online now: Phylogenomics-driven metalloantibiotic engineering: Overcoming ciprofloxacin resistance in Pseudomonas aeruginosa with sideromycin-bismuth synergy

SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism Matmat et al. show that brain-specific methionine synthase deficiency disrupts hippocampal metabolism, mitochondria, and Wnt signaling. Pharmacological activation of SIRT1 with SRT2104 restores metabolic and epigenetic balance, promoting neurogenesis and rescuing memory performance.

Online now: SIRT1 mediates brain metabolic and developmental consequences of methionine synthase deficiency in inborn errors of cobalamin metabolism

Enhancing gastric cancer immunotherapy: Insights from multi-omics analysis and innovations in photodynamic-chemotherapy nanoplatforms Resistance to immune checkpoint blockade limits therapeutic benefit in gastric cancer. Qiu et al. show that tumor-intrinsic YAP1 promotes immunosuppression through a CXCL5-CXCR2-SPP1+ macrophage axis. To target this pathway, they develop a biomimetic nanoplatform that inhibits YAP1 and induces immunogenic cell death, enhancing ICB efficacy in preclinical models.

Online now: Enhancing gastric cancer immunotherapy: Insights from multi-omics analysis and innovations in photodynamic-chemotherapy nanoplatforms

Hierarchically collapsible nanoactuator modulates mitochondrial ferroptosis-bioenergetic homeostasis cascade to decouple ischemic stroke Sun et al. report a hierarchically collapsible nanoactuator that restores mitochondrial function and blocks iron-driven oxidative damage, reducing neuronal injury after stroke. This work highlights a promising direction for improving outcomes in ischemic brain disease.

Online now: Hierarchically collapsible nanoactuator modulates mitochondrial ferroptosis-bioenergetic homeostasis cascade to decouple ischemic stroke

Delayed viral rebound post-ART interruption in infant macaques given SIV-specific neutralizing antibodies Powers and colleagues demonstrate that passive administration of SIV Env RhmAbs just prior to ART interruption in a nonhuman primate model of pediatric HIV infection leads to delayed viral rebound. Increased SIV-specific CD8+ T cells and broadening of neutralization capacity during ART interruption suggest a vaccinal effect of the RhmAbs.

Online now: Delayed viral rebound post-ART interruption in infant macaques given SIV-specific neutralizing antibodies

Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles Enriquez et al. describe a lipid nanoparticle platform for β cell-enriched mRNA delivery. The system delivers functional mRNA to mouse β cells and to human β cells in a xenotransplant model. In a mouse model of autoimmune diabetes, PD-L1 mRNA delivery attenuates insulitis and delays disease progression.

Online now: Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles

Dual PD-1/IL-2Rα targeting restores CD8+ T cell fitness via STAT5/CD47 axis in SMARCA4-deficient NSCLC Shang et al. reveal that the loss of ICAM1 on SMARCA4-deficient tumor cells leads to diminished IL-2 responsiveness and impaired effector function in CD8+ T cells. PD-1/IL-2 bsAb activates IL-2/STAT5/CD47 on CD8+ T cells, shielding them from macrophage-mediated clearance, resulting in enhanced CD8+ T cell survival within the immunosuppressive niche.

Online now: Dual PD-1/IL-2Rα targeting restores CD8+ T cell fitness via STAT5/CD47 axis in SMARCA4-deficient NSCLC

Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease Luo et al. identify PPP2R5C in plasma as an early biomarker of Alzheimer’s disease that declines prior to tau hyperphosphorylation. PPP2R5C modulates tau homeostasis via PP2A activation and ULK1-dependent autophagolysosomal pathways, enabling early diagnosis and providing mechanistic insight into AD pathogenesis.

Online now: Neuronal PPP2R5C in plasma is a potential biomarker for early diagnosis of Alzheimer’s disease

Submit your abstract here

We’re pleased to invite abstracts for presentation @CellSymposia #CSCellDeath26 in Hangzhou, China, October 22–24, 2026. Submit your abstract before June 19 and help shape the future of cell death research.

Submit here: http://dlvr.it/TR6r93

HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer Wang et al. demonstrate that HIF activation in VHL-deficient ccRCC cells primes tumor cells for apoptosis by transcriptionally inducing procaspase-10. DNMT protein degradation by dDNMT unmasks TRAIL signaling, triggering caspase-10-dependent apoptosis. Combining dDNMT with recombinant TRAIL induces robust, selective apoptosis in patient-derived VHL-deficient ccRCC models, revealing an actionable epigenetic vulnerability.

Online now: HIF-activated priming of TRAIL-induced cell death determines epigenetic vulnerability in kidney cancer

Cell therapy for brain tumors: The first 60 years Cellular immunotherapies have been tested for the treatment of primary brain tumors since 1968, with clinical responses observed, albeit limited and inconsistent, from the earliest studies. Mehta et al. review clinical experience with adoptive cell therapies for brain tumors, highlighting key findings from published clinical studies.

Online now: Cell therapy for brain tumors: The first 60 years

Benchmarking large language models for predictive modeling in biomedical research with a focus on reproductive health Sarwal et al. benchmark large language models (LLMs) on four reproductive health prediction tasks from DREAM challenges. Several LLM-generated executable workflows match median participant accuracy and, in one case, outperform top teams. This demonstrates that LLMs can successfully assist with developing predictive machine learning models, while still requiring human oversight.

Online now: Benchmarking large language models for predictive modeling in biomedical research with a focus on reproductive health

Functional human salivary gland organoids for tissue regeneration in chemically defined culture systems Zhang et al. establish a chemically defined system that generates functional human salivary gland organoids. These organoids preserve epithelial diversity, perform key secretory functions, and restore salivary secretion and glandular structure after transplantation, providing a translational platform for treating salivary hypofunction.

Online now: Functional human salivary gland organoids for tissue regeneration in chemically defined culture systems

Chemomechanical remodeling of glucocorticoid-sensitive fibroblasts for multimodal synergistic therapy of skin fibrosis Lu et al. reveal that ECM stiffness induces glucocorticoid resistance in hypertrophic scars by activating the FAK-AKT-HDAC2 pathway. They develop a chemomechanical microneedle platform that remodels the fibrotic niche and resensitizes fibroblasts to therapy, effectively reversing scar progression.

Online now: Chemomechanical remodeling of glucocorticoid-sensitive fibroblasts for multimodal synergistic therapy of skin fibrosis

Enhancing diagnosis of mild cognitive impairment through brain-heart-gut metabolic networks in whole-body PET imaging Li et al. propose a framework integrating brain-heart-gut (BHG) interactions from whole-body PET to enhance the diagnosis of mild cognitive impairment and reveal BHG metabolic connectivity in MCI. Guided by information from peripheral organs, their model achieves diagnostic performance comparable to that of whole-body PET while using solely brain PET data.

Online now: Enhancing diagnosis of mild cognitive impairment through brain-heart-gut metabolic networks in whole-body PET imaging

Tumor microenvironment transcriptional activity enables robust stratification of chemotherapy response in triple-negative breast cancer Dai et al. demonstrate that tumor-specific total mRNA expression (TmS) outperforms existing classifications in stratifying triple-negative breast cancer chemotherapy responses across diverse populations. This deconvolution approach reveals population-specific tumor microenvironment programs and identifies extracellular matrix targeting as a therapeutic strategy for patients with low-TmS.

Online now: Tumor microenvironment transcriptional activity enables robust stratification of chemotherapy response in triple-negative breast cancer