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AI Deception: Risks, Dynamics, and Controls
Gut microbial metabolites in cancer immunomodulation
Mol Cancer. 2025 Dec 3. doi: 10.1186/s12943-025-02521-5. Online ahead of print.
ABSTRACT
Gut microbiota-derived metabolites are emerging as systemic "remote immunoregulators" that shape tumor immunity across tissues. Integrating evidence across short-chain fatty acids, tryptophan derivatives, secondary bile acids, polyamines and other metabolites, we advance a metabolite-immune pathway-cancer framework that links receptor-mediated signaling, epigenetic remodeling and metabolic reprogramming to context-dependent, bidirectional immune effects. Importantly, in addition to the g protein-coupled receptor / aryl hydrocarbon receptor pathway, the selected microbial small molecule metabolites are the true T-cell receptor ligands of unconventional T cells, directly shaping the tissue resident immune and tumor microenvironment, supplementing the receptor signaling and epigenetic programs in our framework. We synthesize how these metabolites recalibrate the tumor immune microenvironment-modulating antigen presentation, T-cell effector fitness and exhaustion, regulatory T-cell activity, and myeloid polarization-and why the same metabolite can either potentiate immune surveillance or entrench immunosuppression depending on ligand-receptor pairing, dose and tissue niche. We compare tumor-type specific patterns (e.g., colorectal, liver, lung, breast and prostate cancers) to highlight common circuits and organ-restricted idiosyncrasies. Methodologically, we outline how single-cell and spatial multi-omics, imaging mass spectrometry and functional biosensors now enable co-registration of metabolite exposure with immune-cell states in human tumors, providing an actionable basis for biomarker discovery. Given ongoing debate about signals attributed to intratumoral microbiota in low-biomass tumor tissues, we foreground quantifiable, spatially mappable and pharmacologically tractable metabolite-receptor pathways, using microbe-associated molecular patterns / translocation as comparators to judge when chemical signals should be prioritized as intervention targets. Finally, we evaluate precision intervention avenues-including fecal microbiota transplantation, rational bacterial consortia, engineered microbes and nanoparticle-enabled metabolite delivery-and propose stratification rules that pair metabolite/receptor signatures with fit-for-purpose delivery. Together, mapping tissue-specific metabolite-immune circuits and embedding them in robust biomarker frameworks may convert microbial metabolites from correlative markers into therapeutic targets and tools, improving the efficacy and durability of cancer immunotherapy.
PMID:41339918 | DOI:10.1186/s12943-025-02521-5
Radiologist Copilot: An Agentic Assistant with Orchestrated Tools for Radiology Reporting with Quality Control
MedCondDiff: Lightweight, Robust, Semantically Guided Diffusion for Medical Image Segmentation
SelfAI: Building a Self-Training AI System with LLM Agents
Human Decision-making is Susceptible to AI-driven Manipulation
Uni-X: Mitigating Modality Conflict with a Two-End-Separated Architecture for Unified Multimodal Models
The AI Productivity Index (APEX)
Decoding the cholesterol-apoptosis axis in HCC: a machine learning-based multi-omics integration and single-cell transcriptomic analysis
Discov Oncol. 2025 Nov 25;16(1):2162. doi: 10.1007/s12672-025-04010-z.
ABSTRACT
Liver hepatocellular carcinoma (LIHC), a predominant form of primary hepatic malignancy, demonstrates a progressively escalating global incidence, imposing substantial health and economic burdens on patients and society. Early diagnosis remains challenging, often resulting in late-stage detection, which limits the efficacy of current therapeutic strategies. This study systematically examines the transcriptional signatures of apoptosis-associated and cholesterol metabolic pathways in LIHC, providing insights into its underlying mechanisms and identifying potential prognostic markers. We employed multi-omics and machine learning to evaluate gene expression variations and construct a prognostic risk scoring model. This study identified apoptosis- and cholesterol metabolism-related differentially expressed genes (ACMRDEGs). Importantly, LASSO regression analysis identified six hub genes (EPHX2, FABP5, SQLE, ADH4, HMGCS2, and CYP7A1) as critical prognostic biomarkers, demonstrating significant correlation with overall survival (OS). Furthermore, immune cell infiltration analysis indicated significant differences in 12 immune cell types within LIHC microenvironment, underscoring the immune system's involvement in disease progression. cholesterol and alcohol metabolism pathways were significantly enriched among hub gene modules, as quantified by multiple gene enrichment analyses. Single-cell analysis identified six major cell types, providing a deeper understanding of the cellular heterogeneity within LIHC. In summarize, this study presents the first integrated apoptosis-cholesterol metabolic pathway-based six-gene prognostic model for LIHC, validated for robustness across multiple cohorts, which may facilitate personalized therapeutic strategies and refined risk assessment in clinical practice.
PMID:41288805 | PMC:PMC12647489 | DOI:10.1007/s12672-025-04010-z
Decoding the cholesterol-apoptosis axis in HCC: a machine learning-based multi-omics integration and single-cell transcriptomic analysis
Discov Oncol. 2025 Nov 25;16(1):2162. doi: 10.1007/s12672-025-04010-z.
ABSTRACT
Liver hepatocellular carcinoma (LIHC), a predominant form of primary hepatic malignancy, demonstrates a progressively escalating global incidence, imposing substantial health and economic burdens on patients and society. Early diagnosis remains challenging, often resulting in late-stage detection, which limits the efficacy of current therapeutic strategies. This study systematically examines the transcriptional signatures of apoptosis-associated and cholesterol metabolic pathways in LIHC, providing insights into its underlying mechanisms and identifying potential prognostic markers. We employed multi-omics and machine learning to evaluate gene expression variations and construct a prognostic risk scoring model. This study identified apoptosis- and cholesterol metabolism-related differentially expressed genes (ACMRDEGs). Importantly, LASSO regression analysis identified six hub genes (EPHX2, FABP5, SQLE, ADH4, HMGCS2, and CYP7A1) as critical prognostic biomarkers, demonstrating significant correlation with overall survival (OS). Furthermore, immune cell infiltration analysis indicated significant differences in 12 immune cell types within LIHC microenvironment, underscoring the immune system's involvement in disease progression. cholesterol and alcohol metabolism pathways were significantly enriched among hub gene modules, as quantified by multiple gene enrichment analyses. Single-cell analysis identified six major cell types, providing a deeper understanding of the cellular heterogeneity within LIHC. In summarize, this study presents the first integrated apoptosis-cholesterol metabolic pathway-based six-gene prognostic model for LIHC, validated for robustness across multiple cohorts, which may facilitate personalized therapeutic strategies and refined risk assessment in clinical practice.
PMID:41288805 | DOI:10.1007/s12672-025-04010-z
From Hypothesis to Publication: A Comprehensive Survey of AI-Driven Research Support Systems
Multimodal analysis of whole slide images in colorectal cancer
npj Digital Medicine, Published online: 24 November 2025; doi:10.1038/s41746-025-02095-y
Multimodal analysis of whole slide images in colorectal cancerGrounded by Experience: Generative Healthcare Prediction Augmented with Hierarchical Agentic Retrieval
SciAgent: A Unified Multi-Agent System for Generalistic Scientific Reasoning
The dual immunomodulatory role of B cells in tumorigenesis: mechanisms, microenvironment crosstalk, and therapeutic implications
Front Immunol. 2025 Oct 30;16:1649812. doi: 10.3389/fimmu.2025.1649812. eCollection 2025.
ABSTRACT
B lymphocytes exhibit a multifaceted and context-dependent role in tumor biology, acting as both promoters and suppressors of malignancy through dynamic interactions within the tumor microenvironment (TME). This review synthesizes current evidence on the dual functions of B cells in tumor immunity, highlighting their capacity to orchestrate antitumor responses via antigen presentation, antibody-dependent cytotoxicity, and tertiary lymphoid structure (TLS)-mediated T cell activation, while paradoxically driving immunosuppression through regulatory B cells (Bregs), pro-angiogenic signaling, and immune checkpoint modulation. Key mechanisms include TLS formation, which enhances cytotoxic T cell priming and correlates with improved immunotherapy outcomes, and Breg-mediated secretion of IL-10/TGF-β, which fosters T cell exhaustion and myeloid-derived suppressor cell recruitment. Tumor-type specificity is evident: TLS-rich malignancies like melanoma and Non-Small Cell Lung Cancer (NSCLC) show B cell-driven immune activation, whereas pancreatic and hepatocellular carcinomas demonstrate B cell functional plasticity influenced by metabolic and epigenetic reprogramming. Therapeutically, B cell-targeted strategies-including CD20 antibodies, CAR-T cells, and B cell epitope vaccines-demonstrate efficacy in hematologic and solid tumors, yet face challenges due to subset heterogeneity and sex-specific response disparities. Emerging approaches combine immune checkpoint inhibitors (ICBs) with TLS-inducing agents or exploit B cell-derived biomarkers for personalized therapy. Future directions emphasize deciphering B cell metabolic-niche crosstalk, optimizing combinatorial regimens, and leveraging spatial multiomics to resolve functional heterogeneity. By bridging mechanistic insights with clinical translation, this work underscores B cells as pivotal regulators of tumor immunity and advocates for precision strategies to harness their antitumor potential while mitigating pro-tumor plasticity.
PMID:41246318 | PMC:PMC12611826 | DOI:10.3389/fimmu.2025.1649812
MedFuse: Multiplicative Embedding Fusion For Irregular Clinical Time Series
Stereo-seq V2: Spatial mapping of total RNA on FFPE sections with high resolution
SciAgent: A Unified Multi-Agent System for Generalistic Scientific Reasoning
Publisher Correction: Deep-learning-based virtual screening of antibacterial compounds
Nature Biotechnology, Published online: 07 November 2025; doi:10.1038/s41587-025-02941-0
Publisher Correction: Deep-learning-based virtual screening of antibacterial compounds