New Insights of CCR7 Signaling in Dendritic Cell Migration and Inflammatory Diseases

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 25, 2022

CCR7, collaborated with its ligands CCL19 and CCL21, controls extensive migratory events in the immune system. CCR7-bearing dendritic cells can swarm into T-cell zones lymph nodes, initiating antigen presentation response. Abnormal expression of CCR7 will cause a series inflammatory diseases due to chaotic cell trafficking. In this review, we take an in-depth look at structural-functional domains trajectory nodes. Then, summarize regulatory network including transcriptional regulation, translational posttranslational internalization, desensitization, recycling. Furthermore, potential strategies targeting regulate migration deal are integrated, which not only emphasizes possibility be target immunotherapy but also has implication on homing benefit diseases.

Language: Английский

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Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization

Bioactive Materials, Journal Year: 2022, Volume and Issue: 18, P. 399 - 408

Published: March 28, 2022

Pathological angiogenesis frequently occurs in tumor tissue, limiting the efficiency of chemotherapeutic drug delivery and accelerating progression. However, traditional vascular normalization strategies are not fully effective limited by development resistance. Herein, inspired intervention endogenous bioelectricity vessel formation, we propose a wireless electrical stimulation therapeutic strategy, capable breaking bioelectric homeostasis within cells, to achieve normalization. Polarized barium titanate nanoparticles with high mechano-electrical conversion performance were developed, which could generate pulsed open-circuit voltage under low-intensity ultrasound. We demonstrated that significantly inhibited endothelial cell migration differentiation vitro. Interestingly, found angiogenesis-related eNOS/NO pathway was inhibited, be attributed destruction intracellular calcium ion gradient stimulation. In vivo tumor-bearing mouse model indicated normalized vasculature optimizing structure, enhancing blood perfusion, reducing leakage, restoring local oxygenation. Ultimately, anti-tumor efficacy combination treatment 1.8 times single doxorubicin group. This work provides strategy based on piezoelectric nanoparticles, is expected safe clinical adjuvant malignant tumors.

Language: Английский

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Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Aug. 9, 2023

Abstract Background Gemcitabine resistance (GR) is a significant clinical challenge in pancreatic adenocarcinoma (PAAD) treatment. Macrophages the tumor immune-microenvironment are closely related to GR. Uncovering macrophage-induced GR mechanism could help devise novel strategy improve gemcitabine treatment outcomes PAAD. Therefore, preclinical models accurately replicating patient properties essential for cancer research and drug development. Patient-derived organoids (PDOs) represent promising vitro model investigating targets, accelerating development, enabling personalized strategies outcomes. Methods To investigate effects of macrophage stimulation on GR, co-cultures were set up using PDOs from three PAAD patients with macrophages. identify signaling factors between macrophages cells (PCCs), 97-target cytokine array TCGA-GTEx database utilized. The analysis revealed CCL5 AREG as potential candidates. role inducing was further investigated data sections obtained 48 over years, inhibitors, short hairpin RNA (shRNA). Furthermore, single-cell sequencing GEO analyzed explore crosstalk PCCs overcome inhibitors targeting macrophage-CCL5-Sp1-AREG feedback loop evaluated cell lines, PDOs, orthotopic mouse carcinoma. Results responsible Macrophage-derived activates CCR5/AKT/Sp1/CD44 axis confer stemness chemoresistance PCCs. PCC-derived promotes secretion through Hippo-YAP pathway. By loop, mithramycin improves outcome results PDO corroborated models, data. Conclusions Our study highlights that superior choice precision medicine. confers facilitate by activating CCR5/AKT/SP1/CD44 combination shows therapeutic treating models.

Language: Английский

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Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 733, P. 150437 - 150437

Published: July 23, 2024

Language: Английский

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A novel antagonist of the CCL5/CCR5 axis suppresses the tumor growth and metastasis of triple-negative breast cancer by CCR5-YAP1 regulation

Cancer Letters, Journal Year: 2024, Volume and Issue: 583, P. 216635 - 216635

Published: Jan. 17, 2024

Language: Английский

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Glioblastoma microenvironment—from biology to therapy

Genes & Development, Journal Year: 2024, Volume and Issue: unknown

Published: May 29, 2024

Glioblastoma (GBM) is the most aggressive primary brain cancer. These tumors exhibit high intertumoral and intratumoral heterogeneity in neoplastic nonneoplastic compartments, low lymphocyte infiltration, abundance of myeloid subsets that together create a highly protumorigenic immunosuppressive microenvironment. Moreover, heterogeneous GBM cells infiltrate adjacent tissue, remodeling neural microenvironment to foster tumor electrochemical coupling with neurons metabolic astrocytes, thereby driving growth. Here, we review its role low-to-high-grade glioma transition, concluding discussion challenges therapeutically targeting outlining future research opportunities.

Language: Английский

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Microglia and monocyte-derived macrophages drive progression of pediatric high-grade gliomas and are transcriptionally shaped by histone mutations

Immunity, Journal Year: 2024, Volume and Issue: 57(11), P. 2669 - 2687.e6

Published: Oct. 11, 2024

Language: Английский

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A novel chemokine‐based signature for prediction of prognosis and therapeutic response in glioma

CNS Neuroscience & Therapeutics, Journal Year: 2022, Volume and Issue: 28(12), P. 2090 - 2103

Published: Aug. 19, 2022

Abstract Aims Gliomas are the primary malignant brain tumor and characterized as striking cellular heterogeneity intricate microenvironment (TME), where chemokines regulate immune cell trafficking by shaping local networks. This study aimed to construct a chemokine‐based gene signature evaluate prognosis therapeutic response in glioma. Methods In this study, 1024 patients (699 from TCGA 325 CGGA database) with clinicopathological information mRNA sequencing data were enrolled. A chemokine was constructed combining LASSO SVM‐RFE algorithm. GO, KEGG, GSVA analyses performed for function annotations of signature. Candidate mRNAs subsequently verified through qRT‐PCR an independent cohort including 28 glioma samples. Then, immunohistochemical staining (IHC), we detected expression immunosuppressive markers explore role immunotherapy Lastly, Genomics Drug Sensitivity Cancer (GDSC) leveraged predict potential drug related Results significantly associated poorer survival, especially glioblastoma, IDH wildtype. It also played prognostic factor both datasets. Moreover, biological predictive indicated positively immune‐relevant pathways, protein expressions (PD‐L1, IBA1, TMEM119, CD68, CSF1R, TGFB1) enriched high‐risk group. glioblastoma cohort, confirmed showed good predictor patients' response. predicted twelve agents higher riskscore. Conclusion all, our results highlighted 4‐chemokine predicting reflected landscape threw light on integrating tailored risk stratification precision therapy glioblastoma.

Language: Английский

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METTL3 knockdown promotes temozolomide sensitivity of glioma stem cells via decreasing MGMT and APNG mRNA stability

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 23, 2023

Chemo-resistance hinders the therapeutic efficacy of temozolomide (TMZ) in treating glioblastoma multiforme (GBM). Recurrence GBM even after combination maximal tumor resection, concurrent radio-chemotherapy, and systemic TMZ applocation is inevitable attributed to high resistance glioma stem cells (GSCs), which can survive, evolve, initiate tissue remodeling, underlying mechanisms GSCs chemo-resistance, have not been fully elucidated up-to-now. Emerging evidence showed that METTL3-mediated N6-methyladenosine (m6A) modification contributed self-renew radio-resistance GSCs, however, its role on maintenance has clarified need further investigations. We found cell viability half-maximal inhibitory concentration (IC50) against significantly decreased underwent serum-induced differentiation adherent growth cells. Besides, METTL3 expression total m6A declined dramatically consistence with differentiation. Knockdown weakened self-renew, proliferation IC50 whereas enhanced induced γH2AX level, indicating upregulation double-strand DNA damage. also mRNA stability two critical repair genes (MGMT APNG) was regulated by modification. In conclusion, we speculated MGMT APNG mRNAs played crucial roles suppression sensitivity suggest a potential new target GBM.

Language: Английский

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