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Reason--Imagine--Act: Closed-Loop LLM Decision Making with World Models for Autonomous Driving
CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells
Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4
Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.Multi-omics integration identifies ribosome biogenesis-active macrophage subpopulation and its key gene GNL2 in driving liver hepatocellular carcinoma progression and mechanisms
Cancer Cell Int. 2026 May 14. doi: 10.1186/s12935-026-04330-2. Online ahead of print.
ABSTRACT
BACKGROUND: Liver hepatocellular carcinoma (LIHC) is a common malignancy, yet the core genes driving its progression and potential therapeutic targets remain insufficiently explored. Ribosome biogenesis (RB) is a critical biological process linked to various cancers; however, its systematic role in LIHC remains unclear.
METHODS: This study integrated LIHC single-cell RNA-Seq, bulk RNA-Seq, and spatial transcriptomic data with ribosome biogenesis-related gene sets to construct a single-cell atlas of LIHC. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to characterize myeloid cell subsets. Furthermore, an LIHC prognostic risk model based on RB-related genes was developed using 117 machine-learning algorithm combinations. Key findings were subsequently corroborated through experimental validation and clinical sample analysis.
RESULTS: We identified a distinct macrophage subpopulation with high ribosome biogenesis activity, termed ribosome biogenesis-active macrophages (RAMs). These cells exhibited strong communication with inflammatory macrophages, potentially mediated by MIF-related receptor-ligand interactions. We further constructed an 8-gene prognostic model (PA2G4, GNL2, PWP1, DDX49, NOC4L, GDI2, CST7, and RCL1), which showed good predictive performance. Drug sensitivity analysis suggested that the high-risk group may be more responsive to several agents, including docetaxel. Among these genes, GNL2 was selected for further investigation. Elevated GNL2 expression was associated with increased stemness features in myeloid cells. Molecular docking analysis identified several candidate compounds with potential binding affinity to GNL2. Functionally, GNL2 knockdown in macrophages reduced TGF-Ξ² and TNF-Ξ± expression and was associated with decreased proliferation, migration, and invasion of LIHC cells.
CONCLUSION: We identified a highly active ribosome biogenesis-macrophage subpopulation (RAM), and constructed a robust risk model to aid in the diagnosis, prognosis, and treatment of LIHC. GNL2 is associated with increased expression of TGF-Ξ² and TNF-Ξ± and may contribute to LIHC progression.
PMID:42135716 | DOI:10.1186/s12935-026-04330-2
Integrating clinical and multiomics evidence based on disease module theory: deciphering the comorbidity network of psoriasis vulgaris via the Ising model for mechanistic insights
Front Immunol. 2026 Apr 14;17:1744789. doi: 10.3389/fimmu.2026.1744789. eCollection 2026.
ABSTRACT
Psoriasis vulgaris (PV), a chronic immune-mediated inflammatory dermatosis, is associated with a significant burden of systemic comorbidities. Traditional comorbidity research methods struggle to reveal its complex interconnectedness. Based on large-scale retrospective cohort data, we constructed a PV comorbidity network using the Ising model from statistical physics. Weighted network centrality analysis was used to identify core and hub nodes and elucidate shared molecular mechanisms at the multiomics level (nontargeted proteomics and lipid peroxidation metabolomics). Finally, the impact of IL-17A inhibition (IL-17Ai) on PV and atherosclerosis (assessed by carotid Doppler color ultrasound) was evaluated using a prospective intervention study. The Ising model identified atherosclerosis- coronary heart disease (CHD) as the core comorbidity (degree centrality >10), with pulmonary nodules, hypertension, and fatty liver serving as key hub nodes (betweenness centrality >60). Multiomics analysis revealed a core molecular mechanism in PV, involving immune inflammation, oxidative stress, lipid metabolism disorder, and coagulation abnormalities, where the oxidative stress molecule GPX3 acts as a critical hub. Following IL-17Ai intervention, both skin lesions and early atherosclerosis markers significantly improved, accompanied by downregulation of the proinflammatory peripheral blood factor S100A9 and upregulation of anti-inflammatory lipid peroxidation metabolites (e.g., 17(R)-RVD1). This study systematically revealed the modular hierarchical structure of PV comorbidities at the network topology and molecular mechanism levels, confirming the central role of the IL-17 signaling pathway in driving the comorbidity network. This conclusion was further clinically validated by IL-17Ai intervention outcomes. This research provides theoretical and clinical evidence for early identification, prioritized management, and "one drug, multiple targets" therapeutic strategies for treating PV comorbidities.
PMID:42058202 | PMC:PMC13121148 | DOI:10.3389/fimmu.2026.1744789