Suppressive immune microenvironment and CART therapy for glioblastoma: Future prospects and challenges DOI Creative Commons
Jie Lu,

Wen Huo,

Yingze Ma

и другие.

Cancer Letters, Год журнала: 2024, Номер 600, С. 217185 - 217185

Опубликована: Авг. 12, 2024

Glioblastoma, a highly malignant intracranial tumor, has acquired slow progress in treatment. Previous clinical trials involving targeted therapy and immune checkpoint inhibitors have shown no significant benefits treating glioblastoma. This ineffectiveness is largely due to the complex immunosuppressive environment of Glioblastoma cells exhibit low immunogenicity strong heterogeneity microenvironment replete with inhibitory cytokines, numerous cells, insufficient effective T cells. Fortunately, recent Phase I CART for glioblastoma confirmed its safety, small subset patients achieving survival benefits. However, continues face challenges, including blood-brain barrier obstruction, antigen loss, an tumor (TME). article provides detailed examination glioblastoma's microenvironment, both from intrinsic extrinsic cell factors, reviews current basic research on multi-targets treatment, concludes by outlining key challenges using therapy.

Язык: Английский

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

Wenxiang Hong,

Bo Yang, Qiaojun He

и другие.

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Фев. 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.

Язык: Английский

Процитировано

56
Wireless electrical stimulation at the nanoscale interface induces tumor vascular normalization DOI Creative Commons
Changhao Li,

Cairong Xiao,

Lizhen Zhan

и другие.

Bioactive Materials, Год журнала: 2022, Номер 18, С. 399 - 408

Опубликована: Март 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.

Язык: Английский

Процитировано

43
Macrophage-organoid co-culture model for identifying treatment strategies against macrophage-related gemcitabine resistance DOI Creative Commons
Shengwei Jiang,

Tingwei Deng,

Huan Cheng

и другие.

Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)

Опубликована: Авг. 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.

Язык: Английский

Процитировано

34
A novel antagonist of the CCL5/CCR5 axis suppresses the tumor growth and metastasis of triple-negative breast cancer by CCR5-YAP1 regulation DOI
Ling Chen, Guiying Xu,

Xiaoxu Song

и другие.

Cancer Letters, Год журнала: 2024, Номер 583, С. 216635 - 216635

Опубликована: Янв. 17, 2024

Язык: Английский

Процитировано

10
Thermal proteome profiling (TPP) reveals NAMPT as the anti-glioma target of phenanthroindolizidine alkaloid PF403 DOI Creative Commons
Fangfei Li, Zhaoxin Zhang,

Qinyan Shi

и другие.

Acta Pharmaceutica Sinica B, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors DOI Creative Commons
Leire Bejarano, João Lourenço,

Annamaria Kauzlaric

и другие.

Immunity, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

1
Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer DOI

Cora E Miracle,

Chelsea L. McCallister,

Richard D Egleton

и другие.

Biochemical and Biophysical Research Communications, Год журнала: 2024, Номер 733, С. 150437 - 150437

Опубликована: Июль 23, 2024

Язык: Английский

Процитировано

9
Glioblastoma microenvironment—from biology to therapy DOI Open Access
Renee Read, Zoe M. Tapp, Prajwal Rajappa

и другие.

Genes & Development, Год журнала: 2024, Номер unknown

Опубликована: Май 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.

Язык: Английский

Процитировано

7
A novel chemokine‐based signature for prediction of prognosis and therapeutic response in glioma DOI Creative Commons
Wenhua Fan, Di Wang, Guanzhang Li

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2022, Номер 28(12), С. 2090 - 2103

Опубликована: Авг. 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.

Язык: Английский

Процитировано

24
Targeting CCL5 signaling attenuates neuroinflammation after seizure DOI Creative Commons
Zhuoran Zhang, Yan Li, Shihe Jiang

и другие.

CNS Neuroscience & Therapeutics, Год журнала: 2022, Номер 29(1), С. 317 - 330

Опубликована: Ноя. 28, 2022

Abstract Background Epilepsy is a neurological condition that causes unprovoked, recurrent seizures. Accumulating evidence from clinical and experimental studies indicates neuroinflammation exacerbates seizure activity. Methods We investigated the transcriptional changes occurring in specific brain domains of mouse model, using 10× Genomics spatial transcriptomics. Differential gene expression pathway analysis were applied to investigate potential signaling targets for seizure, including CCL5/CCR5 pathway. Maraviroc, an FDA‐approved C‐C chemokine receptor 5 (CCR5) antagonist, was used verify impact mice. Results found distinguished regional transcriptome features hippocampus The exhibited unique inflammatory signatures, glia activation, apoptosis, immune response Especially, we observed notable ligand (CCL5) throughout entire hippocampus. Blockade via maraviroc prevented microglia activation neuron degeneration Conclusions This study supports targeting after seizure.

Язык: Английский

Процитировано

24