Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.

ABSTRACT

Transformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy remains the gold standard for confirming histologic transformation, whereas molecular profiling and liquid biopsy may facilitate early detection and longitudinal disease monitoring. Platinum-etoposide remains the most commonly used clinical standard after transformation, but its benefit is typically transient and durable disease control remains uncommon. Continuation of EGFR tyrosine kinase inhibitors combined with chemotherapy may prolong progression-free survival in selected patients but has not consistently improved overall survival. Anti-angiogenic therapy, particularly anlotinib, and chemo-immunotherapy have shown encouraging activity in selected patients, while emerging strategies targeting DLL3, MYC, SOX2, and epigenetic regulators may broaden the therapeutic landscape. Prospective studies integrating repeat tissue sampling, comprehensive genomic profiling, biomarker-guided patient stratification, pharmacogenomics, functional drug-sensitivity testing where feasible, and integrated multi-omics approaches are needed to advance molecularly guided and individualized treatment for T-SCLC.

PMID:42724635 | PMC:PMC13560167 | DOI:10.3389/fmed.2026.1865050

Front Med (Lausanne). 2026 Aug 27;13:1865050. doi: 10.3389/fmed.2026.1865050. eCollection 2026.

ABSTRACT

Transformed small-cell lung cancer (T-SCLC) is a clinically important form of histologic transformation and a mechanism of acquired resistance in non-small-cell lung cancer (NSCLC). It is associated with poor prognosis, with a median overall survival of only about 9-13 months. This review summarizes recent advances in the mechanisms, diagnosis, monitoring, and treatment of T-SCLC. Repeat biopsy remains the gold standard for confirming histologic transformation, whereas molecular profiling and liquid biopsy may facilitate early detection and longitudinal disease monitoring. Platinum-etoposide remains the most commonly used clinical standard after transformation, but its benefit is typically transient and durable disease control remains uncommon. Continuation of EGFR tyrosine kinase inhibitors combined with chemotherapy may prolong progression-free survival in selected patients but has not consistently improved overall survival. Anti-angiogenic therapy, particularly anlotinib, and chemo-immunotherapy have shown encouraging activity in selected patients, while emerging strategies targeting DLL3, MYC, SOX2, and epigenetic regulators may broaden the therapeutic landscape. Prospective studies integrating repeat tissue sampling, comprehensive genomic profiling, biomarker-guided patient stratification, pharmacogenomics, functional drug-sensitivity testing where feasible, and integrated multi-omics approaches are needed to advance molecularly guided and individualized treatment for T-SCLC.

PMID:42724635 | PMC:PMC13560167 | DOI:10.3389/fmed.2026.1865050

Cell Rep. 2026 Sep 3;45(9):117943. doi: 10.1016/j.celrep.2026.117943. Online ahead of print.

ABSTRACT

Metabolic alterations are increasingly recognized during influenza virus infection, but how local lactate accumulation shapes antiviral immunity remains poorly characterized. By integrating time-series targeted energy metabolomics, single-cell RNA sequencing, flow cytometry, and functional perturbation, we show that influenza virus infection preferentially increases lactate within the lung microenvironment, where it restrains pulmonary CD8⁺ T cell response. Mechanistically, extracellular lactate enters dendritic cells through monocarboxylate transporter (MCT)-dependent transport and induces a tolerogenic-like state marked by impaired maturation, reduced costimulation, and diminished CD8⁺ T cell-priming capacity. Direct experimental evidence identifies H3K18la as a prominent lactate-responsive histone lactylation mark, while multi-omics integration links it to enhancer accessibility and NRF2 pathway activation. Functional studies further show that NRF2 promotes dendritic cell suppression by reinforcing tolerogenic programs and limiting mtROS-dependent XBP1 splicing. Together, these findings reveal a lactate-driven histone lactylation-NRF2 pathway that modulates antiviral immunity during influenza infection.

PMID:42690934 | DOI:10.1016/j.celrep.2026.117943

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

Immunotargets Ther. 2026 Mar 17;15:541852. doi: 10.2147/ITT.S541852. eCollection 2026.

ABSTRACT

PURPOSE: NUP85 encodes protein components of the Nup107-160 subunit of the nuclear pore complex, belonging to the Nucleoporins (NUPs) family, potentially implicating its role in human cancer. This study aims to elucidate the potential involvement of NUP85 in cancer pathogenesis.

METHODS: Leveraging data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), Cancer Cell Line Encyclopedia (CCLE), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), CellMiner, and GeneMANIA databases, we investigated the role of NUP85 across various tumors. Correlations between NUP85 expression and pathological stage, histological grade, survival, immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), drug resistance, DNA methylation, copy number variation (CNV), and single-cell expression were analyzed. Gene functional enrichment analysis was conducted to explore NUP85-associated pathways. Molecular biology experiments including Western blotting, flow cytometry, trans-well migration, and invasion assays were performed to validate NUP85's oncogenic role in lung adenocarcinoma (LUAD) and oral squamous cell carcinoma (OSCC) cell lines.

RESULTS: Our findings reveal up-regulated expression of NUP85 in most tumor tissues, with significant correlations observed with pathological stage, survival, immune infiltration, TMB, MSI, drug resistance, DNA methylation, and CNV. Molecular biology experiments confirm NUP85's tumor-promoting role in LUAD and OSCC cell lines. Single-cell sequencing data suggest elevated NUP85 expression primarily in proliferative T cells (Tprolif).

CONCLUSION: NUP85 emerges as a potential tumor marker associated with tumor immunity and poor prognosis. These insights offer avenues for the development of novel therapeutic targets and anti-neoplastic drugs.

PMID:41869435 | PMC:PMC13005628 | DOI:10.2147/ITT.S541852

Gut. 2026 Mar 30:gutjnl-2025-337938. doi: 10.1136/gutjnl-2025-337938. Online ahead of print.

ABSTRACT

BACKGROUND: Survival outcomes after transarterial chemoembolisation (TACE) vary in hepatocellular carcinoma (HCC) patients, and existing prognostic scores and imaging models often lack generalisability and biological interpretability.

OBJECTIVE: To develop and validate a multimodal prognostication model for HCC that allows for a precise assessment of survival outcomes of HCC patients receiving TACE therapy.

DESIGN: This study enrolled 1448 HCC patients, including a TACE cohort (n=1349), a biomarker subset from a randomised trial (n=41), a single-cell RNA sequencing cohort and The Cancer Genome Atlas (TCGA) HCC cohort (n=50). Pre-treatment contrast-enhanced CT images were used to construct deep learning and conventional radiomic models. The early-fusion and late-fusion models (LFMs) were compared, and a clinical-radiologic model (CRM) was formed by integrating the better-performing LFM with clinical variables. Using TCGA data and single-cell transcriptomic profiles, the differences between high-score and low-score groups in tumour immune microenvironment, cellular functional states and key signalling pathways were investigated.

RESULTS: The CRM effectively stratified patients' survival across multiple independent cohorts and achieved more granular risk stratification than the existing clinical models. Multi-omic analyses revealed that in the LFM high-score group, myelocytomatosis oncogene was activated, epithelial-mesenchymal transition enhanced, glycolysis upregulated and hypoxia pathway activated. Single-cell transcriptomic data confirmed that virtually all cell types in high-risk patients scored high in hypoxia, and cytotoxic T cells had a reduced cytotoxic activity.

CONCLUSION: The CRM model can non-invasively predict the prognosis of HCC patients treated by TACE therapy.

PMID:41856522 | DOI:10.1136/gutjnl-2025-337938

Cell Commun Signal. 2026 Mar 14. doi: 10.1186/s12964-026-02793-4. Online ahead of print.

NO ABSTRACT

PMID:41826981 | DOI:10.1186/s12964-026-02793-4