Tumor cell senescence-induced macrophage CD73 expression is a critical metabolic immune checkpoint in the aging tumor microenvironment

Theranostics, Journal Year: 2024, Volume and Issue: 14(3), P. 1224 - 1240

Published: Jan. 1, 2024

Background:The role of senescent cells in the tumor microenvironment (TME) is usually bilateral, and diverse therapeutic approaches, such as radiotherapy chemotherapy, can induce cellular senescence.Cellular interactions are widespread TME, reprogram immune metabolically by producing metabolites.However, how remodel metabolism TME remains unclear.This study aimed to explore precise targets enhance cells-induced anti-tumor immunity from a metabolic perspective. Methods:The vivo senescence model was induced 8 Gy×3 or cisplatin vitro 10 Gy-irradiation treatment.Metabonomic analysis ELISA assay on interstitial fluid were performed for metabolites screening.Marker expression cell infiltration analyzed flow cytometry.Cell co-culture system senescence-conditioned medium used crosstalk validation vitro.RNA sequencing rescue experiments conducted mechanism excavation.Immunofluorescence staining single-cell transcriptome profiling clinical validation.Results: We innovatively reveal landscape characterized with elevation adenosine.It attributed cell-induced CD73 upregulation tumor-associated macrophages (TAMs).CD73 TAMs evoked SASP-related pro-inflammatory cytokines, especially IL-6, regulated JAK/STAT3 pathway.Consistently, positive correlation between identified lung cancer specimens databases.Lastly, blocking background suppresses tumors activates CD8 + T cell-mediated antitumor immunity.Conclusions: expressed contributes significantly adenosine accumulation suggesting targeting novel synergistic strategy aging microenvironment.

Language: Английский

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Glioma–Immune Cell Crosstalk in Tumor Progression

Cancers, Journal Year: 2024, Volume and Issue: 16(2), P. 308 - 308

Published: Jan. 11, 2024

Glioma progression is a complex process controlled by molecular factors that coordinate the crosstalk between tumor cells and components of microenvironment (TME). Among these, immune play critical role in cancer survival progression. The interplay TME influences outcome immunotherapy other anti-cancer therapies. Here, we present an updated view pro- anti-tumor activities main myeloid lymphocyte cell populations glioma TME. We review underlying mechanisms involved enable gliomas to evade system co-opt these for growth. Lastly, discuss current experimental therapeutic options being developed revert immunosuppressive activity Knowledge elapses may help develop new combination treatments able overcome evasion enhance response immunotherapies.

Language: Английский

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Τ cell-mediated adaptive immunity in the transition from metabolic dysfunction-associated steatohepatitis to hepatocellular carcinoma

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: May 7, 2024

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressed version of metabolic steatotic liver disease (MASLD) characterized by inflammation and fibrosis, but also a pathophysiological "hub" that favors emergence malignancies. Current research efforts aim to identify risk factors, discover biomarkers, aid patient stratification in context MASH-induced hepatocellular carcinoma (HCC), most prevalent cancer among MASLD patients. To investigate tumorigenic transition HCC, researchers predominantly exploit preclinical animal-based MASH models studies based on archived human biopsies clinical trials. Recapitulating immune response during tumor development progression vital obtain mechanistic insights into HCC. Notably, advanced complexity behind pathogenesis shifted focus towards innate immunity, fundamental element hepatic niche usually altered robustly course disease. During last few years, however, there has been an increasing interest for deciphering role adaptive immunity particularly regarding functions various T cell populations. effectively understand specific cells HCC development, scientists should urgently fill current knowledge gaps this field. Pinpointing signature, sketching landscape, characterizing cellular interactions dynamics within MASH-HCC are essential unravel mechanisms exploits enable cancer. end, our review aims summarize state linked

Language: Английский

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Pyrimidine compounds BY4003 and BY4008 inhibit glioblastoma cells growth via modulating JAK3/STAT3 signaling pathway

Neurotherapeutics, Journal Year: 2024, Volume and Issue: 21(5), P. e00431 - e00431

Published: Aug. 16, 2024

Glioblastoma (GBM) is a brain tumor characterized by its aggressive and invasive properties. It found that STAT3 abnormally activated in GBM, inhibiting signaling can effectively suppress progression. In this study, novel pyrimidine compounds, BY4003 BY4008, were synthesized to target the JAK3/STAT3 pathway, their therapeutic efficacy mechanisms of action evaluated compared with Tofacitinib U251, A172, LN428 patient-derived glioblastoma cells. The ADP-Glo™ kinase assay was utilized assessed inhibitory effects BY4008 on JAK3, crucial member JAK family. results showed both compounds significantly inhibited JAK3 enzyme activity, IC

Language: Английский

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Association of immunoglobulin E levels with glioma risk and survival

JNCI Journal of the National Cancer Institute, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Previous epidemiologic studies have reported an association of serum immunoglobulin E (IgE) levels with reduced glioma risk, but the between IgE and prognosis has not been characterized. This study aimed to examine how sex, tumor subtype, class modulate risk survival.

Language: Английский

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Targeting JAK/STAT3 in glioblastoma cells using an alginate-PNIPAm molecularly imprinted hydrogel for the sustained release of ruxolitinib

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: unknown, P. 140025 - 140025

Published: Jan. 1, 2025

Language: Английский

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Peptide‑based therapeutic strategies for glioma: current state and prospects

Peptides, Journal Year: 2025, Volume and Issue: 185, P. 171354 - 171354

Published: Feb. 6, 2025

Language: Английский

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Pan-cancer analysis of the disulfidptosis-related gene RPN1 and its potential biological function and prognostic significance in gliomas

Heliyon, Journal Year: 2024, Volume and Issue: 10(11), P. e31875 - e31875

Published: May 25, 2024

BackgroundNumerous studies have shown a strong correlation between disulfidptosis and various cancers. However, the expression function of RPN1, crucial gene in disulfidptosis, remain unclear context cancer.MethodsGene clinical information on lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) Genotype-Tissue Expression (GTEx) databases. RPN1 was analyzed using Timer2.0 Human Protein (HPA) Prognostic significance assessed Cox regression analysis Kaplan–Meier curves. Genetic mutations methylation levels examined cBioPortal UALCAN platforms, respectively. relationship tumor mutation burden (TMB) microsatellite instability (MSI) across different cancer types Spearman coefficient. immune cell infiltration database, whereas variations drug sensitivity explored CellMiner database. Receiver operating characteristic curves validated RPN1's diagnostic potential glioma, its with checkpoint inhibitors (ICIs) Spearman's Single-sample set enrichment elucidated link cells pathways. In addition, nomogram based developed to predict patient prognosis. functional impact glioma confirmed scratch Transwell assays.ResultRPN1 aberrantly expressed cancers affected main type amplified. exhibited positive myeloid-derived suppressor cells, neutrophils, macrophages, negative CD8+ T hematopoietic stem cells. associated TMB MSI positively correlated multiple ICIs gliomas. also into microenvironment. an independent prognostic factor for gliomas, demonstrated excellent predictive performance. Interference reduces migratory invasive ability cells.ConclusionRPN1 exerts multifaceted effects stages cancer, including infiltration, prognosis, treatment outcomes. affects prognosis microenvironment patients making target glioma.

Language: Английский

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Hypoxia-inducible factor 1alpha and vascular endothelial growth factor in Glioblastoma Multiforme: a systematic review going beyond pathologic implications

Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Journal Year: 2024, Volume and Issue: 32(8), P. 1239 - 1256

Published: Jan. 1, 2024

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by extensive heterogeneity and vascular proliferation. Hypoxic conditions in the tissue microenvironment are considered a pivotal player leading progression. Specifically, hypoxia known to activate inducible factors, such as hypoxia-inducible factor 1alpha (HIF-1α), which turn can stimulate neo-angiogenesis through activation of various downward mediators, endothelial growth (VEGF). Here, we aimed explore role HIF-1α/VEGF immunophenotypes alone combination with other prognostic markers or clinical image analysis data, potential biomarkers GBM prognosis treatment efficacy. We performed systematic review (Medline/Embase, Pubmed database search was completed 16th April 2024 two independent teams; PRISMA 2020). evaluated methods immunoassays, cell viability, animal patient survival retrieved studies assess unbiased data. used inclusion criteria, evaluation based on expression, imaging manifestations related application immunoassays for protein effectiveness therapeutic strategies expression. exclusion data not reporting both HIF-1α VEGF prognosis. included 50 investigating total 1319 human specimens, 18 different lines GBM-derived stem cells, 6 models, identify association immunophenotypes, macroscopic approaches. found that increased expression correlates oncogenic miR-210-3p, Oct4, AKT, COX-2, PDGF-C, PLDO3, M2 polarization, ALK, unfavorable survival. Reduced FIH-1, ADNP, STAT1 upregulation, well manifestations, like epileptogenicity, favorable GBM. Based our may be useful tool clarify MRI-PET distinguishing between progression pseudoprogression. Finally, reflect efficacy, including combined first-line histone deacetylase inhibitors, thimerosal, active metabolite irinotecan, STAT3 inhibitors alone, resulting These were supported variable evaluate immunophenotypes. Data limitations include use less sensitive detection some cases. Overall, support HIF-1α/VEGF's

Language: Английский

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Targeting STAT3 for Cancer Therapy: Focusing on Y705, S727, or Dual Inhibition?

Cancers, Journal Year: 2025, Volume and Issue: 17(5), P. 755 - 755

Published: Feb. 23, 2025

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that strongly implicated in various cancers. In its canonical signaling pathway, Janus kinases (JAKs) phosphorylate STAT3 at the Y705 residue response to cytokines or growth factors, with pY705 serving as key marker oncogenic activity. Elevated levels correlate poor prognosis, numerous small-molecule inhibitors have been developed block this phosphorylation site. More recently, S727 (pS727) has emerged critical contributor STAT3-mediated oncogenesis, particularly due role mitochondrial translocation. Evidence suggests pS727 may even surpass driving These findings prompt an important question: Which should be prioritized for effective inhibition cancer therapy? This review compiles critically analyzes current literature on targeting and/or pS727, evaluating their therapeutic efficacy vitro, vivo, clinical trials. We assess unique effects each downstream signaling, toxicity, outcomes. Our analysis indicates both achieve greatest effectiveness. However, associated higher toxicity risks. Comprehensive evaluation underscores importance maximum benefit. The also shows co-targeting increase overall efficacy. approached lower affinity minimize enhance feasibility dual-targeting strategies.

Language: Английский

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