Advancements in osteosarcoma management: integrating immune microenvironment insights with immunotherapeutic strategies

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Июнь 10, 2024

Osteosarcoma, a malignant bone tumor predominantly affecting children and adolescents, presents significant therapeutic challenges, particularly in metastatic or recurrent cases. Conventional surgical chemotherapeutic approaches have achieved partial efficacy; however, the prognosis for long-term survival remains bleak. Recent studies highlighted imperative comprehensive exploration of osteosarcoma immune microenvironment, focusing on integration diverse immunotherapeutic strategies—including checkpoint inhibitors, microenvironment modulators, cytokine therapies, antigen-specific interventions, cancer vaccines, cellular antibody-based treatments—that are directly pertinent to modulating this intricate microenvironment. By targeting cells, activating host responses, these innovative demonstrated substantial potential enhancing effectiveness treatments. Although most novel strategies still research clinical trial phases, they already individuals with osteosarcoma, suggesting possibility developing new, more personalized effective treatment options. This review aims provide overview current advancements immunotherapy, emphasizing significance integrating various methods optimize outcomes. Additionally, it underscores subsequent further investigate interactions between system, aiming devise strategies. The present comprehensively addresses landscape delineating crucial scientific concerns thereby outlining directions.

Язык: Английский

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Bevacizumab induces ferroptosis and enhances CD8+ T cell immune activity in liver cancer via modulating HAT1 and increasing IL-9

Acta Pharmacologica Sinica, Год журнала: 2024, Номер 45(9), С. 1951 - 1963

Опубликована: Май 17, 2024

Язык: Английский

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Donor Substitution Engineering of Hemicyanine Nanoparticles to Reprogram the Tumor Microenvironment and Enhance Fn14‐Targeted BiTE for Glioblastoma Photoimmunotherapy

Advanced Functional Materials, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Glioblastoma (GBM) is a highly malignant intracranial tumor with limited treatment options. Bispecific T‐cell engagers (BiTEs) are being explored for GBM treatment, but their success hindered by inadequate T cell infiltration and activation due to the acidic immunosuppressive microenvironment. Photothermal immunotherapy lyses tumors activates immune responses, complementing BiTEs. This study innovatively employs donor engineering strategy develop hemicyanine dyes (Hcys) that emit from near‐infrared (NIR) I NIR II. The Hcy excellent properties encapsulated in an amphiphilic micelle, forming nano assembly lactate oxidase (PLH1100). PLH1100 exhibits spectral absorption at 980 nm, photothermal conversion efficiency of 58.7%, capability NIR‐II imaging. Besides ablation, regulates lactic acid metabolism immunogenic death, improving microenvironment promoting activation. Further studies demonstrate effectively kills human murine cells, inhibits orthotopic U87 growth BALB/c‐nu mice, enhances efficacy Fn14‐targeted BiTE GL261 C57BL/6 achieving synergistic “1+1>2” therapeutic effect. Collectively, this work opens new pathway using Hcy‐based molecules combined drugs therapy, significant clinical potential.

Язык: Английский

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Tumor Vascular Normalization by B7-H3 Blockade Augments T Lymphocyte-Mediated Antitumor Immunity

European Journal of Pharmacology, Год журнала: 2025, Номер unknown, С. 177334 - 177334

Опубликована: Фев. 1, 2025

Язык: Английский

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Prognostic risk modeling of endometrial cancer using programmed cell death-related genes: a comprehensive machine learning approach

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Март 8, 2025

Endometrial cancer represents a significant health challenge, with rising incidence and complex prognostic challenges. This study aimed to develop robust predictive model integrating programmed cell death-related genes advanced machine learning techniques. Utilizing transcriptomic data from TCGA-UCEC GSE119041 datasets, we employed comprehensive approach involving 117 algorithms. Key methodologies included differential gene expression analysis, weighted co-expression network functional enrichment studies, immune landscape evaluation, multi-dimensional risk stratification. We identified 10 critical (PTGIS, TIMP3, SRPX, SNCA, HIC1, BAK1, STXBP2, TRIB3, RTKN2, E2F1) constructed superior performance. The StepCox[forward] + plsRcox algorithm combination demonstrated excellent accuracy (AUC > 0.8). Kaplan–Meier analysis revealed survival differences between high- low-risk groups in both training (HR = 3.37, p < 0.001) validation cohorts 2.05, 0.021). showed strong correlations clinical characteristics, infiltration patterns, potential therapeutic responses. presents novel, endometrial prognosis, molecular insights provide more precise stratification tool translation.

Язык: Английский

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Combined anti-PD-L1 and anti-VEGFR2 therapy promotes the antitumor immune response in GBM by reprogramming tumor microenvironment

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 3, 2025

Abstract Inhibitors of programmed cell death ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) are commonly used in the clinic, but they beneficial for only a minority glioblastoma multiforme (GBM) patients. GBM has significant immunosuppressive properties, there many cells dysfunctional effector T tumor microenvironment (TME), which is one important reasons failure clinical treatment GBM. Here, we have identified P21 activated kinase 4 (PAK4) as pivotal immune suppressor TME. PAK4 threonine protein kinase, knockdown attenuates abnormalities promotes T-cell infiltration. In this study, our results showed that expression was significantly downregulated after VEGFR2 knockdown. Next, constructed coculture system CD8+ cells. Our findings combined anti-PD-L1 anti-VEGFR2 therapy can regulate TME inhibit cells' escape; overexpression reverse effect. Finally, tested combination mouse intracranial graft models found prolong survival. These suggest downregulate PAK4, reprogram by increasing cytotoxic infiltration activation, enhance therapeutic effect on

Язык: Английский

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ROS impairs tumor vasculature normalization through an endocytosis effect of caveolae on extracellular SPARC

Cancer Cell International, Год журнала: 2023, Номер 23(1)

Опубликована: Авг. 1, 2023

Abstract Background The accumulation of reactive oxygen species (ROS) in tumor microenvironment (TME) is an important player for tumorigenesis and progression. We aimed to explore the outcomes ROS on vessels potential regulated mechanisms. Methods Exogenous H 2 O was adopted simulate setting. Immunofluorescence staining ultrasonography were used assess vascular endothelial coverage perfusions tumors inoculated with Lewis lung cancer (LLC) melanoma (B16F10) cells C57BL/6 mice, respectively. ELISA western-blot detect expression secreted acidic cysteine-rich protein (SPARC) Caveale-1 human umbilical vein (HUVEC) extra- intracellularly. Intracellular translocation SPARC observed using electron microscopy immunofluorescence approaches. Result Under context oxidative stress, pericyte recruitment neovascularization mouse tissues would be aberrated, which subsequently led disruption architecture perfusion dysfunction. In vitro, HUVEC extracellularly down-regulated, whereas intracellularly it up-regulated. By staining, we that might undergo transmembrane transport via caveale-1-mediated endocytosis. Finally, binding phosphorylated-caveale-1 also detected B16F10 tissues. Conclusion stress environment, within occurs structural deterioration decreased capacity. One main regulatory mechanisms migration extracellular from endothelium intracellular compartments Caveolin-1 carriers.

Язык: Английский

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Regulation, maintenance, and remodeling of high endothelial venules in homeostasis, inflammation, and cancer

Current Opinion in Physiology, Год журнала: 2023, Номер 36, С. 100705 - 100705

Опубликована: Авг. 18, 2023

High endothelial venules (HEVs), high walled cuboidal blood vessels, through their expression of adhesion molecules and chemokines, allow the entrance lymphoid cells into primary, secondary, tertiary structures (aka organs). HEV heterogeneity exists between various organs in peripheral node addressin (PNAd) mucosal vascular molecule 1(MAdCAM-1). Transcriptomic analyses reveal extensive heterogeneity, plasticity, regulation gene ontogeny, acute inflammation, chronic inflammation within organs. Rules regulating development are flexible inflammation. HEVs tumor diagnostic favorable clinical outcome response to Immunotherapy, including immune check point blockade. Immunotherapy induces provides an for naïve, central memory, effector a niche stem like precursor cells. Understanding will permit exploitation as routes drug delivery autoimmune lesions, rejecting organs, tumors.

Язык: Английский

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Integrated immunogenomic analyses of single-cell and bulk profiling construct a T cell-related signature for predicting prognosis and treatment response in osteosarcoma

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 22, 2024

T cells play a crucial role as regulators of anti-tumor activity within the tumor microenvironment (TME) and are closely associated with progression osteosarcoma (OS). Nevertheless, specific cell-related genes (TCRGs) in pathogenesis OS remains unclear. First, we processed single-cell RNA sequencing (scRNA-seq) data from public databases performed cell annotation. We identified highly variable each type using "FindAllMarkers" function, explored distribution different clusters, investigated inter-cellular communication patterns via "CellChat" framework. Then, used multivariate Cox analysis to construct TCRG developed nomogram predict survival probabilities for patients. Finally, validated aforementioned results various lines immune infiltration, expression checkpoints, chemotherapy sensitivity, efficacy targeted therapies across risk groups. From scRNA-seq data, 3,000 genes, presented top 10 core lines.Moreover, our delved into interactions between other types. Our analyses constructed predictive signature (TCRS) that incorporated these prognostic TCRGs, showing clear separation high-risk low-risk patient groups multiple cohorts. Survival indicated better outcomes patients classified group. The group exhibited elevated levels CD4 memory resting cells, contrasting higher macrophage M0 observed CIBERSORT algorithm. Furthermore, exhibitedAQ1 significant up-regulation checkpoint (ICGs) lower Tumour Immune Dysfunction Exclusion (TIDE) scores, suggesting they may be suitable immunotherapy. Conversely, appeared more responsive therapies, according drug sensitivity analysis. In conclusion, study TCRS OS, assessed response These findings provide novel insights personalized treatment strategies potentially guiding effective therapeutic interventions.

Язык: Английский

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Enhanced cytotoxicity in multiple myeloma via T cells armed with bispecific T cell engager targeting B-cell maturation antigen on cancer cells and CD3 on T cells

International Immunopharmacology, Год журнала: 2024, Номер 143, С. 113480 - 113480

Опубликована: Окт. 30, 2024

Язык: Английский

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