Cell Reports Medicine

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

DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response Peng et al. show that tumor-promoting and tumor-restraining fibroblast subtypes, defined by the single-sample classifier DeCAF, shape cancer progression and immunotherapy response across multiple tumor types. DeCAF subtypes reveal multidimensional interactions with tumor subtypes and immune cells, providing a clinically meaningful framework for predicting outcomes and guiding treatment strategies.

Online now: DeCAF defines clinical fibroblast subtypes and multidimensional tumor-stroma crosstalk shaping prognosis and immunotherapy response

Syndecan-1-targeted therapeutic antibody impairs macropinocytosis and elicits antitumor immunity in pancreatic cancer We identify SDC1 as a key driver of PDAC progression and resistance to KRAS inhibitors and develop a therapeutic-grade antibody that suppresses tumor growth. The anti-SDC1 mAb blocks macropinocytosis, induces ADCC, and synergizes with chemotherapy, KRAS inhibitors, and immunotherapies, establishing SDC1 targeting as a promising PDAC therapy.

Online now: Syndecan-1-targeted therapeutic antibody impairs macropinocytosis and elicits antitumor immunity in pancreatic cancer

Spatial single-cell analysis reveals tumor microenvironment signatures predictive of oral cavity cancer outcome Identifying those patients who progress to fatal disease after surgical treatment of early-stage OSCC is an unmet clinical need. Using TME proteomic single-cell analyses, Näsiaho et al. discover that proliferating LECs at the tumor’s invasive margin serve as a clinically measurable independent adverse prognostic biomarker in two independent patient cohorts.

Online now: Spatial single-cell analysis reveals tumor microenvironment signatures predictive of oral cavity cancer outcome

A conserved eIF1A+ luminal cell-centered hypoxic and “cold” tumor microenvironment promotes pan-subtype prostate cancer progression Cheng et al. describe the conserved features across different histological subtypes of prostate cancer at proteomic level using imaging mass cytometry. Spatial analyses indicate that eIF1A+ luminal cells are associated with hypoxia response and immunologically “cold” microenvironment. Targeting eIF1A and translation holds potential for clinical intervention in prostate cancer.

Online now: A conserved eIF1A+ luminal cell-centered hypoxic and “cold” tumor microenvironment promotes pan-subtype prostate cancer progression

Targeting BCMA in multiple myeloma with a trifunctional NK cell engager Tang et al. describe SAR’514, an NK cell engager targeting BCMA in multiple myeloma. This trifunctional molecule demonstrates potent anti-tumor activity in vitro and in vivo with minimal cytokine release and efficiently activates patient NK cells against myeloma cells, including those not responding to daratumumab.

Online now: Targeting BCMA in multiple myeloma with a trifunctional NK cell engager

A revised staging system for natural killer/T cell lymphoma incorporating skull base invasion and nasal/non-nasal subtype distinction Cao et al. develop a revised staging system for natural killer/T cell lymphoma that incorporates skull base invasion (SBI) and nasal/non-nasal subtypes. This work demonstrates improved prognostic accuracy and a more balanced stage distribution, with implications for clinical risk stratification in the modern treatment era.

Online now: A revised staging system for natural killer/T cell lymphoma incorporating skull base invasion and nasal/non-nasal subtype distinction

Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis Yao et al. identify a brain-based glucose control mechanism in which the metabolic enzyme MDH2 acts as a signaling brake on oxytocin neurons. Inhibiting MDH2 activates thermogenic fat via neural pathways to normalize high blood glucose, revealing a noninvasive strategy inspired by bariatric surgery.

Online now: Hypothalamic malate dehydrogenase 2 modulates systemic glucose metabolism through oxytocin-mediated thermogenesis

The Ca2+ sensor STIM1 promotes neuronal ferroptosis by regulating iron homeostasis to exacerbate brain injury after intracerebral hemorrhage Zhang et al. reveal that STIM1 promotes neuronal ferroptosis and exacerbates brain injury by interacting with the iron uptake protein TFR1 after intracerebral hemorrhage. S-IN-1 inhibits STIM1-TFR1 binding and exhibits neuroprotective effects, offering a promising therapeutic strategy.

Online now: The Ca2+ sensor STIM1 promotes neuronal ferroptosis by regulating iron homeostasis to exacerbate brain injury after intracerebral hemorrhage

Choroid plexus enlargement associates with serum neurofilament and predicts relapse-free progression in multiple sclerosis In this multicenter longitudinal study, Fleischer et al. show that enlargement of the choroid plexus, a key gateway between the blood and cerebrospinal fluid, signals early neuroaxonal injury and predicts silent progression in MS. Their findings suggest that volumetric changes at this barrier contribute to neurodegeneration and clinical disability in MS.

Online now: Choroid plexus enlargement associates with serum neurofilament and predicts relapse-free progression in multiple sclerosis