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Embracing Trustworthy Brain-Agent Collaboration as Paradigm Extension for Intelligent Assistive Technologies
Multi-omics analyses inform mechanisms of immunotherapy response in pancreatic cancer
Front Immunol. 2025 Oct 2;16:1673098. doi: 10.3389/fimmu.2025.1673098. eCollection 2025.
ABSTRACT
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) continues to exhibit resistance to immunotherapy. In this study, we evaluated the efficacy of combining immunotherapy with chemotherapy for the treatment of advanced pancreatic cancer. Additionally, we employed a multimodal analytical approach to elucidate the immune landscape and conduct transcriptomic profiling in PDAC.
METHODS: A retrospective analysis was conducted on the clinical data of 52 patients diagnosed with advanced PDAC who underwent a combined treatment regimen of immunotherapy and chemotherapy. The study evaluated the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). To characterize the immune landscape in treatment-naive pancreatic ductal adenocarcinoma (PDAC) tumors and in the systemic circulation, flow cytometry, multiplex immunohistochemistry (mIHC), and whole transcriptome sequencing were employed.
RESULTS: The study reported an ORR of 32.7%, a DCR of 67.3%, and a 6-month PFS rate of 38.5%, with a median PFS of 5.5 months. Patients treated with a combination of immunotherapy and gemcitabine achieved the longest PFS. The first-line treatment cohort exhibited a significantly higher DCR (79.3% vs. 52.2%, P = 0.038) and a longer median PFS (6.6 vs. 3.5 months, P = 0.032) compared to the second-line treatment cohort. The efficacy of treatment varied depending on the drug combinations used. Flow cytometry analysis revealed a greater frequency of CD45- CD64+ cells in the peripheral blood of patients with progressive disease (PD) compared to those with a partial response (PR). Multiplex immunofluorescence (MIF) analysis indicated an increased intratumoral infiltration of CD8+ T cells and CD137+ CD8+ T cells in patients with PR. Whole transcriptome sequencing (WTSS) identified key genes involved in immune regulation, signal transduction, and digestive function. Hemopexin (HPX) and regulatory factor X-associated protein (RFXAP) were upregulated in PR patients and showed a positive correlation with survival, whereas Interleukin-6 (IL-6) expression was linked to poor prognosis.
CONCLUSIONS: These findings indicate that immunochemotherapy shows potential for the treatment of advanced PDAC. Our study elucidates the immune landscape associated with PDAC and provides critical insights for the identification of prospective therapeutic targets, which could guide the development of innovative combination immunotherapy strategies.
PMID:41112307 | PMC:PMC12528169 | DOI:10.3389/fimmu.2025.1673098
Integrative single-cell and multi-omics analyses reveal ferroptosis-associated gene expression and immune microenvironment heterogeneity in gastric cancer
Discov Oncol. 2025 Jan 17;16(1):57. doi: 10.1007/s12672-025-01798-8.
ABSTRACT
Gastric cancer (GC), a prevalent malignancy worldwide, encompasses a multitude of biological processes in its progression. Recently, ferroptosis, a novel mode of cell demise, has become a focal point in cancer research. The microenvironment of gastric cancer is composed of diverse cell populations, yet the specific gene expression profiles and their association with ferroptosis are not well understood. Our study employed single-cell RNA sequencing to thoroughly investigate the transcriptomic profiles and identify differential gene expression in gastric cancer, offering fresh insights into the cellular diversity and underlying molecular mechanisms of this disease. We discovered a set of significantly differentially expressed genes in GC, which may serve as valuable leads for future functional investigations. Subsequent analyses, including gene set intersection and functional enrichment, pinpointed genes implicated in ferroptosis and conducted comprehensive Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to elucidate their biological roles. In the gene selection and model validation section, critical genes were identified using machine learning algorithms, constructing a model with high predictive accuracy. Besides, distorted immune landscapes were further identified in RBL using ssGSEA analysis such that the complex association of gene expression features and its interaction networks as well as infiltration by various types of immune cells can be more clearly understood. Correlation analysis with different immune cell subtypes showed CTSB as an important regulator in the distributions of cancer infiltrating cells. Single-cell RNA sequencing analysis was utilized to map the cellular composition and gene expression profiles of cells in the gastric cancer microenvironment, which provide critical information for elucidating cellular heterogeneity as well as tumor microenvironment regulation in GC. Moreover, the distribution of FTH1, ZFP36 and CIRBP at different expression levels show new research prospects for functional information of these promoters in tumor microenvironment. In summary, the present study augments our knowledge of molecular mechanisms underlying gastric tumorigenesisa and provide scientific basis for identifing new targets and biomarkers in therapeutic diagnosis.
PMID:39831925 | PMC:PMC11747029 | DOI:10.1007/s12672-025-01798-8
Hypoxia-induced epigenetic regulation of miR-485-3p promotes stemness and chemoresistance in pancreatic ductal adenocarcinoma via SLC7A11-mediated ferroptosis
Cell Death Discovery, Published online: 29 May 2024; doi:10.1038/s41420-024-02035-x
Hypoxia-induced epigenetic regulation of miR-485-3p promotes stemness and chemoresistance in pancreatic ductal adenocarcinoma via SLC7A11-mediated ferroptosis