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An engineered nanopore identifies saccharides, amino acids, peptides and ribonucleotides
Nature Biotechnology, Published online: 14 September 2026; doi:10.1038/s41587-026-03308-9
Modified nanopore simultaneously identifies diverse biomolecules and their modifications.CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis
Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.
ABSTRACT
Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.
PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3
Integrated single-cell multi-omics characterization reveals lipid-associated macrophage-mediated immunosuppression in neoadjuvant immunotherapy of hepatocellular carcinoma
Nat Commun. 2026 Jul 31;17(1):9381. doi: 10.1038/s41467-026-75949-y.
ABSTRACT
Hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality rate. Although immune checkpoint inhibitors (ICIs) improved survival outcomes for HCC patients, limited objective response rate highlights the urgency of investigating determinants of immunotherapy. Here, we explore HCC resistance mechanisms following neoadjuvant αPD-1 immunotherapy by constructing a comprehensive multi-modal single-cell transcriptomic atlas consisting of 14 HCC patients treated with αPD-1 from our cohort (ClinicalTrials.gov ID: NCT06571396) and 60 external HCC cases with heterogeneous treatment backgrounds. Supervised by clinical outcomes of our cohort, we identify positive and negative regulators of immunotherapy within the tumor immune microenvironment (TIME), especially lipid-associated macrophages (LAM) with increased lipid metabolic state in non-responders and characterized by C1QA, FABP1, and APOA1 expression. We further show the presence, exogenous inducements and immunosuppressive functions of LAM, along with regulation strategies of its lipid-associated condition, including lycopene and chiglitazar. Furthermore, we construct interaction networks of immune regulators across responders and non-responders, showing distinct ligand-receptor landscapes with intervention targets. We reveal the TIME components including immunosuppressive LAMs that influence immunotherapy outcomes, thus providing evidence and insights for exploring immune landscape and therapeutic strategies for HCC immunotherapy. ClinicalTrials.gov ID: NCT06571396.
PMID:42680737 | PMC:PMC13534469 | DOI:10.1038/s41467-026-75949-y
ConceptM$^3$oE: Concept-Guided Multimodal Mixture of Experts for Interpretable Computational Pathology
Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics
HISA: Efficient Hierarchical Indexing for Fine-Grained Sparse Attention
Accelerating Diffusion Large Language Models with SlowFast Sampling: The Three Golden Principles
Gene regulatory landscape dissected by single-cell four-omics sequencing
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10322-z
Combining single-cell parallel profiling of genome conformation, histone modifications, chromatin accessibility and gene expression reveals dynamics and intranuclear spatial clustering of epigenome profiles, enabling sophisticated analysis of the regulatory landscape across cell types and tissues.Multi-omics analysis reveals AR as a potential prognostic factor and immune-related therapeutic target in gastric cancer
Biochem Biophys Rep. 2026 Mar 16;46:102537. doi: 10.1016/j.bbrep.2026.102537. eCollection 2026 Jun.
ABSTRACT
BACKGROUND: Although studies have shown that the androgen receptor (AR) is associated with tumor progression and malignant regulation, its role in the tumor immune microenvironment and predictive value for prognosis and immunotherapy response in various cancer types have not been systematically analyzed.
METHODS: In this paper, multi-omics techniques was used to analyze AR comprehensively.
RESULTS: A comprehensive pan-cancer analysis revealed that the AR was expressed in a variety of tumors, especially as a risk factor for poor prognosis in gastric cancer. In addition, gene set enrichment analysis showed that the AR promotes cell proliferation and tumor cell invasion and regulates anti-tumor response. Immune score, immune cell infiltration, and anticancer immune cycle analysis showed that high AR levels were correlated with low infiltration of CD4+ T cells and NKT cells, high infiltration of Th2 cells and MDSCs, negatively correlated with antigen-presenting molecules, and positively correlated with various immune-negative regulatory molecules. Single-cell sequencing highlighted the heterogeneous expression of ARs in different cell types, particularly in epithelial cells, where high AR levels were associated with the enhanced activity of tumor-promoting pathways.
CONCLUSIONS: In conclusion, this study highlights the potential of the AR as a novel biomarker for gastric cancer prognosis and immunotherapy efficacy, expanding its applicability in the development of new antitumor drugs.
PMID:41890218 | PMC:PMC13014673 | DOI:10.1016/j.bbrep.2026.102537