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Received β€” 4 December 2025 ⏭ Favourites

Gut microbial metabolites in cancer immunomodulation

βœ‡Omics In Lung
By: Hengshuo Liu Β· Xingyu Xiong Β· Weizhen Zhu Β· Sheng Wang Β· Weichao Huang Β· Guoqing Zhu Β· Hang Xu Β· Lu Yang
3 December 2025 at 19:00

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

Received β€” 19 September 2025 ⏭ Favourites

Diagnostic Performance of Computed Tomography–Based Artificial Intelligence for Early Recurrence of Cholangiocarcinoma: Systematic Review and Meta-Analysis

βœ‡Journal of Medical Internet Research
By: Jie Chen Β· Jianxin Xi Β· Tianyu Chen Β· Lulu Yang Β· Kaijia Liu Β· Xiaobo Ding
19 September 2025 at 04:30
Background: Despite artificial intelligence (AI) models demonstrating high predictive accuracy for early cholangiocarcinoma recurrence, their clinical application faces challenges, such as reproducibility, generalizability, hidden biases, and uncertain performance across diverse datasets and populations, raising concerns about their practical applicability. Objective: This meta-analysis aims to systematically assess the diagnostic performance of AI models using computed tomography (CT) imaging to predict early recurrence of cholangiocarcinoma. Methods: A systematic search was conducted in PubMed, Embase, and Web of Science for studies published up to May 2025. Studies were selected based on the Participants, Index test, Target condition, Reference standard, Outcomes, and Setting (PITROS) framework. Participants included patients diagnosed with cholangiocarcinoma (including intrahepatic and extrahepatic locations). The index test was AI techniques applied to CT imaging for early recurrence prediction (defined as within 1 year), while the target condition was early recurrence of cholangiocarcinoma (positive group: recurrence; negative group: no recurrence). The reference standard was pathological diagnosis or imaging follow-up confirming recurrence. Outcomes included sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC), assessed in both internal and external validation cohorts. The setting comprised retrospective or prospective studies using hospital datasets. Methodological quality was assessed using an optimized version of the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool. Heterogeneity was assessed using the IΒ² statistic. Pooled sensitivity, specificity, DOR, and AUC were calculated using a bivariate random-effects model. Results: A total of 9 studies with 30 datasets involving 1537 patients were included. In internal validation cohorts, CT-based AI models showed a pooled sensitivity of 0.87 (95% CI 0.81-0.92), specificity of 0.85 (95% CI 0.79-0.89), DOR of 37.71 (95% CI 18.35-77.51), and AUC of 0.93 (95% CI 0.90-0.94). In external validation cohorts, pooled sensitivity was 0.87 (95% CI 0.81-0.91), specificity was 0.82 (95% CI 0.77-0.86), DOR was 30.81 (95% CI 18.79-50.52), and AUC was 0.85 (95% CI 0.82-0.88). The AUC was significantly lower in external validation cohorts compared to internal validation cohorts (P<.001). Conclusions: Our results show that CT-based AI models predict early cholangiocarcinoma recurrence with high performance in internal validation sets and moderate performance in external validation sets. However, the high heterogeneity observed may impact the robustness of these results. Future research should focus on prospective studies and establishing standardized gold standards to further validate the clinical applicability and generalizability of AI models.
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