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
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
Citations
2
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
Citations
1
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
Citations
0
Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(5)
Published: April 28, 2025
Abstract Background Gastric cancer (GC) exhibits high heterogeneity that relies on the oncogenic properties of cells and multicellular interactions in tumour microenvironment. However, GC their molecular characteristics are still largely unexplored. Methods We employed single‐cell spatial transcriptomics to comprehensively map intra‐tumoural within GC. Additionally, vitro experiments, clinical sample analyses, patient‐derived organoid models (PDOs) were conducted validate key interaction patterns between tumor stromal cells. Results Seven robust meta‐programs (MP1–MP7) defined with distinct biological significance distributions. MP3 MP4 intimately associated CD8 T skewed toward a cytotoxic or exhaustion state, while MP7, characterised by highest degree malignancy, harboured an immune lockdown microenvironment around it spatially myofibroblasts (myCAFs). Notably, we clarified interplay MP7 myCAFs, where induces chemotactic migration fibroblasts promoting transformation into myCAFs via GDF15/TGFBR2, turn, myCAFs‐derived RSPO3 up‐regulates EGR1 promote human PDOs. Ultimately, accumulation led fewer infiltration cells, resulting immune‐deprived diminished efficacy immunotherapy. based gene expression signatures predicted specific drugs verified more potent inhibitory effects Taselisib Lapatinib for than conventional at same concentration. Conclusion Taken together, these results deepened understanding paved way novel therapeutic strategies targeting loop treatment. Key points (MP1‐MP7) identified gastric cancer. was strongly correlated metastasis poor survival patients. promoted fibroblast creating MyCAFs induced RSPO3/EGR1 pathway, cell migration. inhibitors
Language: Английский
Citations
0
ACS Omega, Journal Year: 2025, Volume and Issue: unknown
Published: May 11, 2025
Language: Английский
Citations
0
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
Citations
3