Signature Construction Associated with Tumor-Infiltrating Macrophages Identifies IRF8 as a Novel Biomarker for Immunotherapy in Advanced Gastric Cancer

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1089 - 1089

Published: Jan. 27, 2025

Advanced gastric cancer (AGC) is characterized by poor prognosis and limited responsiveness to immunotherapy. Tumor-associated macrophages (TAMs) play a pivotal role in progression therapeutic outcomes. In this study, we developed novel gene signature associated with M1-like TAMs using data from the Gene Expression Omnibus (GEO) The Cancer Genome Atlas (TCGA) predict immunotherapy response. This was determined as an independent prognostic indicator for AGC, high-risk patients exhibiting immunosuppressive tumor immune microenvironment (TIME) poorer survival Furthermore, Interferon regulatory factor 8 (IRF8) identified key validated through vitro vivo experiments. IRF8 overexpression reshaped suppressive TIME, leading increased presence of TAMs, IFN-γ+ CD8+ T cells, Granzyme B+ cells. Notably, combination anti-PD-1 therapy significantly inhibited growth syngeneic mouse models. AGC elevated expression were found be more responsive treatment. These findings highlight potential biomarkers evaluation offering insights that could guide personalized treatment strategies.

Language: Английский

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Cancer stem cells and tumor-associated macrophages as mates in tumor progression: mechanisms of crosstalk and advanced bioinformatic tools to dissect their phenotypes and interaction

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 6, 2025

Cancer stem cells (CSCs) are a small subset within the tumor mass significantly contributing to cancer progression through dysregulation of various oncogenic pathways, driving growth, chemoresistance and metastasis formation. The aggressive behavior CSCs is guided by several intracellular signaling pathways such as WNT, NF-kappa-B, NOTCH, Hedgehog, JAK-STAT, PI3K/AKT1/MTOR, TGF/SMAD, PPAR MAPK kinases, well extracellular vesicles exosomes, molecules cytokines, chemokines, pro-angiogenetic growth factors, which finely regulate CSC phenotype. In this scenario, microenvironment (TME) key player in establishment permissive niche, where engage intricate communications with diverse immune cells. "oncogenic" mainly represented B T lymphocytes, NK cells, dendritic Among macrophages exhibit more plastic adaptable phenotype due their different subpopulations, characterized both immunosuppressive inflammatory phenotypes. Specifically, tumor-associated (TAMs) create an milieu production plethora paracrine factors (IL-6, IL-12, TNF-alpha, TGF-beta, CCL1, CCL18) promoting acquisition stem-like, invasive metastatic TAMs have demonstrated ability communicate via direct ligand/receptor (such CD90/CD11b, LSECtin/BTN3A3, EPHA4/Ephrin) interaction. On other hand, exhibited capacity influence creating favorable for progression. Interestingly, bidirectional TME leads epigenetic reprogramming sustains malignant transformation. Nowadays, integration biological computational data obtained cutting-edge technologies (single-cell RNA sequencing, spatial transcriptomics, trajectory analysis) has improved comprehension biunivocal multicellular dialogue, providing comprehensive view heterogeneity dynamics CSCs, uncovering alternative mechanisms evasion therapeutic resistance. Moreover, combination biology will lead development innovative target therapies dampening CSC-TME Here, we aim elucidate most recent insights on complex interactions specifically TAMs, tracing exhaustive scenario from primary

Language: Английский

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Comprehensive analysis and experimental validation of disulfidptosis-associated prognostic signature and immune microenvironment characterization of gastric cancer

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(4)

Published: Feb. 25, 2025

Gastric cancer (GC) is one of the most common causes cancer-related death worldwide. As a novel form programmed cell death, disulfidptosis characterized by excessive cysteine accumulation, disulfide stress and actin destruction. There evidence that targeting promising anticancer strategy. Further improvement GC risk stratification based on has positive clinical significance. We analyzed expression levels disulfidptosis-associated genes (DPAGs) in normal tissues molecular subtypes patients. Based characteristics DPAG subtypes, differentially expressed prognosis-related were selected LASSO-univariate Cox analysis multivariate to establish prognostic model. Using single-cell sequencing reveals subpopulation for GC. The function target was verified vitro experimental means, including siRNA, qRT-PCR, Western blot, CCK-8, Transwell assay. score be an independent factor significantly associated with poor prognosis gastric cancer. Subsequent studies subgroup immunoinfiltration characteristics, drug sensitivity analysis, immunotherapy response somatic mutation comprehensively confirmed potential guiding significance individualized treatment Single-cell revealed DPAG-related signatures across subpopulations. In experiments showed APC11, as DPAGs, highly cancer, knockdown APC11 could inhibit proliferation migration cells, demonstrating reliability bioinformatics results. results this study provide new perspective exploring role occurrence development

Language: Английский

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Identification of potential novel targets for treating inflammatory bowel disease using Mendelian randomization analysis

International Journal of Colorectal Disease, Journal Year: 2024, Volume and Issue: 39(1)

Published: Oct. 16, 2024

Inflammatory bowel disease (IBD) is a complex autoimmune disorder, although some medications are available for its treatment. However, the long-term efficacy of these drugs remains unsatisfactory. Therefore, there need to develop novel drug targets IBD

Language: Английский

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