❌

Normal view

Multimodal AI generates virtual population for tumor microenvironment modeling

GigaTIME leverages multimodal AI to generate virtual multiplex immunofluorescence (mIF) profiles from standard H&E slides, enabling comprehensive tumor immune microenvironment modeling across a large (>14,000) and diverse patient population. This virtual approach unlocks new opportunities for large-scale clinical discoveries that were previously hindered by the scarcity of mIF data.

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

Embracing the Future of Medical Education With Large Language Model–Based Virtual Patients: Scoping Review

Background: In recent years, large language models (LLMs) have experienced rapid development. LLM-based virtual patients have begun to gain attention, offering new opportunities for simulations in medical education. Objective: This study aims to systematically analyze the current applications, research trends, and challenges of LLM-based virtual patients in medical education and to explore potential future directions for development. Methods: This study adheres to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. Five databases (Web of Science Core Collection, PubMed, IEEE Xplore, Embase, and Scopus) were searched from January 1, 2018, to June 24, 2025, to identify studies related to the application of LLM-based virtual patients in medical education. A comprehensive analysis of LLM-based virtual patients from research design to application and evaluation was conducted. Results: A total of 28 studies were included in this scoping review. Analysis revealed that 92.9% (26/28) of the studies were published in the past 2 years, indicating that LLM-based virtual patient research is still in its early stages. The research primarily focuses on medical training and spans a wide range of medical disciplines. When using LLMs, advanced technologies such as social robots, virtual reality, and mixed reality are used to present LLM-based virtual patients. Combining these technologies with various supplementary tools enhances the realism of LLM-based virtual patients and improves user interaction. The evaluation of LLM-based virtual patients mainly emphasizes user experience. However, evaluation methods lack standardization, and only 13% (3/23) of studies used validated tools in assessing LLM-based virtual patients, while only 21.7% (5/23) of studies objectively measured learning outcomes facilitated by LLM-based virtual patients. All included studies expressed a positive attitude toward LLM-based virtual patients; however, they overlook privacy and security considerations in practical applications. Conclusions: LLM-based virtual patients hold significant innovation potential in medical education and are still in the early stages of development. They are primarily applied in medical training and show promise in communication skills training, although they cannot replace real-world interactions. Moreover, the heterogeneity of research designs, the absence of nonverbal cues in interactions, and concerns regarding privacy and security limit their broader implementation. Future research should focus on improving the reliability, realism, safety, and scientific efficacy of LLM-based virtual patients. Trial Registration: Open Science Framework Registries 10.17605/OSF.IO/DMC9Q; https://osf.io/DMC9Q/overview

A whole-slide foundation model for digital pathology from real-world data

Nature, Published online: 22 May 2024; doi:10.1038/s41586-024-07441-w

Prov-GigaPath, a whole-slide pathology foundation model pretrained on a large dataset containing around 1.3 billion pathology images, attains state-of-the-art performance in cancer classification and pathomics tasks.
❌