A Cascade Nanozyme with Amplified Sonodynamic Therapeutic Effects through Comodulation of Hypoxia and Immunosuppression against Cancer

ACS Nano, Год журнала: 2021, Номер 16(1), С. 485 - 501

Опубликована: Дек. 28, 2021

The tumor microenvironment (TME) featured by immunosuppression and hypoxia is pivotal to cancer deterioration metastasis. Thus, regulating the TME improve cell ablation efficiency has received extensive interest in oncotherapy. However, reverse alleviate simultaneously are major challenges for effective therapy. Herein, a multifunctional platform based on Au nanoparticles carbon dots modified hollow black TiO2 nanosphere (HABT-C) with intrinsic cascade enzyme mimetic activities prepared reversing alleviating TME. HABT-C NPs possess triple-enzyme activity act as self-cascade nanozymes, which produce sufficient oxygen generate abundant ROS. theoretical analysis demonstrates that facilitates absorption of H2O O2, separation electron–holes, generation ROS, consequently amplifying sonodynamic therapy (SDT) efficiency. Specifically, exhibits favorable inhibition immunosuppressive mediator expression, along infiltrating immune effector cells into As result, can effectively kill via eliciting infiltration, hypoxia, improving SDT This nanozyme-based (HABT-C@HA) will provide strategy highly efficient against modulation

Язык: Английский

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Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

JCI Insight, Год журнала: 2022, Номер 7(18)

Опубликована: Авг. 9, 2022

Immune checkpoint blockade (ICB) therapy has achieved breakthroughs in the treatment of advanced non–small cell lung cancer (NSCLC). Nevertheless, low response due to immuno-cold (i.e., tumors with limited tumor-infiltrating lymphocytes) tumor microenvironment (TME) largely limits application ICB therapy. Based on glycolytic/cholesterol synthesis axis, a stratification framework for EGFR-WT NSCLC was developed summarize metabolic features and immuno-hot tumors. The cholesterol subgroup displays worst prognosis NSCLC, significant enrichment gene signature, indicating that targeting is essential NSCLC. Statin, inhibitor synthesis, can suppress aggressiveness vitro vivo also drastically reverse phenotype an inflamed vivo. This change led higher Moreover, both our in-house data meta-analysis further support statin significantly enhance efficacy. In terms preliminary mechanisms, could transcriptionally inhibit PD-L1 expression induce ferroptosis cells. Overall, we reveal significance demonstrate improved therapeutic efficacy combination statin. These findings provide clinical insight treat patients

Язык: Английский

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FAM family gene prediction model reveals heterogeneity, stemness and immune microenvironment of UCEC

Frontiers in Molecular Biosciences, Год журнала: 2023, Номер 10

Опубликована: Май 19, 2023

Background: Endometrial cancer (UCEC) is a highly heterogeneous gynecologic malignancy that exhibits variable prognostic outcomes and responses to immunotherapy. The Familial sequence similarity (FAM) gene family known contribute the pathogenesis of various malignancies, but extent their involvement in UCEC has not been systematically studied. This investigation aimed develop robust risk profile based on FAM genes (FFGs) predict prognosis suitability for immunotherapy patients. Methods: Using TCGA-UCEC cohort from Cancer Genome Atlas (TCGA) database, we obtained expression profiles FFGs 552 35 normal samples, analyzed patterns relevance 363 genes. samples were randomly divided into training test sets (1:1), univariate Cox regression analysis Lasso conducted identify differentially expressed (FAM13C, FAM110B, FAM72A) significantly associated with prognosis. A scoring system was constructed these three characteristics using multivariate proportional regression. clinical potential immune status CiberSort, SSGSEA, tumor dysfunction rejection (TIDE) algorithms. qRT-PCR IHC detecting levels 3-FFGs. Results: Three FFGs, namely, FAM13C, FAM72A, identified as strongly effective predictors Multivariate demonstrated developed model an independent predictor UCEC, patients low-risk group had better overall survival than those high-risk group. nomogram scores exhibited good power. Patients higher mutational load (TMB) more likely benefit Conclusion: study successfully validated novel biomarkers predicting can accurately assess facilitate identification specific subgroups who may personalized treatment chemotherapy.

Язык: Английский

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BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity

Advanced Science, Год журнала: 2023, Номер 10(8)

Опубликована: Янв. 15, 2023

Abstract To improve response rate of monotherapy immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, validated that BCAT2 shapes a noninflamed TME bladder cancer. The outcomes multiomics indicate has inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal secretion CD8 + T‐cell‐related chemokines keeps robust negative correlation with BCAT2, generating decreasing tendency T cells around from far near. Cotreatment deficiency anti‐PD‐1 antibody synergistic vivo, implying the potential Moreover, value predicting efficacy immunotherapy multiple cohorts. Together, as key molecule TME, ICB biomarker guiding precision

Язык: Английский

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Integrated multiomics analysis and machine learning refine molecular subtypes and prognosis for muscle-invasive urothelial cancer

Molecular Therapy — Nucleic Acids, Год журнала: 2023, Номер 33, С. 110 - 126

Опубликована: Июнь 5, 2023

Muscle-invasive urothelial cancer (MUC), characterized by high aggressiveness and significant heterogeneity, is currently lacking highly precise individualized treatment options. We used a computational pipeline to synthesize multiomics data from MUC patients using 10 clustering algorithms, which were then combined with machine learning algorithms identify molecular subgroups of resolution develop robust consensus learning-driven signature (CMLS). Through clustering, we identified three subtypes (CSs) that are related prognosis, CS2 exhibiting the most favorable prognostic outcome. Subsequent screening enabled identification 12 hub genes constitute CMLS predictive power for prognosis. The low-CMLS group exhibited more prognosis greater responsiveness immunotherapy was likely exhibit "hot tumor" phenotype. high-CMLS had poor lower likelihood benefitting immunotherapy, but dasatinib romidepsin may serve as promising treatments them. Comprehensive analysis can offer important insights further refine classification MUC. Identification represents valuable tool early prediction patient potential candidates benefit broad implications clinical practice.

Язык: Английский

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Leveraging mitochondrial-programmed cell death dynamics to enhance prognostic accuracy and immunotherapy efficacy in lung adenocarcinoma

Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(10), С. e010008 - e010008

Опубликована: Окт. 1, 2024

Lung adenocarcinoma (LUAD) is a highly heterogeneous disease, posing significant challenges to accurate prognosis prediction. Mitochondria play central role in the energy metabolism of eukaryotic cells and can influence programmed cell death (PCD) mechanisms, which are critical tumorigenesis cancer progression. However, prognostic significance interplay between mitochondrial function PCD LUAD requires further investigation.

Язык: Английский

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Novel post-translational modification learning signature reveals B4GALT2 as an immune exclusion regulator in lung adenocarcinoma

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(2), С. e010787 - e010787

Опубликована: Фев. 1, 2025

Background Lung adenocarcinoma (LUAD) presents significant challenges in prognosis and treatment efficacy evaluation. While post-translational modifications are known to influence tumor progression, their prognostic value LUAD remains largely unexplored. Methods We developed a modification learning signature (PTMLS) using machine techniques, analyzing data from 1231 patients across seven global cohorts. The signature’s predicting immunotherapy response was evaluated 12 cohorts spanning multiple cancer types (n=1201). An in-house tissue cohort (n=171) used validate beta-1,4-galactosyltransferase 2’s (B4GALT2’s) significance. role of B4GALT2 immune exclusion investigated through vivo vitro experiments. Results established PTMLS exhibited exceptional predictive capabilities patient outcomes, surpassing the 98 existing indicators. system’s validated diverse malignancy categories for immunotherapeutic assessment. From biological perspective, correlations were observed between immunological parameters, whereby elevated levels characterized by attenuated responses immunologically cold neoplastic features. Within framework, identified as crucial molecular component (r=0.82, p<0.05), its heightened expression linked unfavorable clinical outcomes cases, particularly specimens exhibiting CD8-depleted phenotypes. spatial distribution patterns cell populations, specifically CD8+ T lymphocytes CD20+ B lymphocytes, elucidated multiplexed immunofluorescence analysis. Laboratory investigations subsequently B4GALT2’s regulatory on cellular expansion both laboratory cultures animal models. Significantly, suppression found enhance lymphocyte populations functional status, thereby potentiating anti-programmed death protein 1 studies. This phenomenon reduced CD62L+CD8 alongside GZMB+/CD44+/CD69+CD8 populations. Conclusion system represents an effective instrument individualized evaluation stratification identification previously unrecognized oncogenic factor involved novel therapeutic avenue optimization.

Язык: Английский

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Ferroptosis‐related gene signature predicts prognosis and immunotherapy in glioma

CNS Neuroscience & Therapeutics, Год журнала: 2021, Номер 27(8), С. 973 - 986

Опубликована: Май 10, 2021

Glioma is a highly invasive brain tumor, which makes prognosis challenging and renders patients resistant to various treatments. Induction of cell death promising in cancer therapy. Ferroptosis, recently discovered regulated death, can be induced for killing glioma cells. However, the prognostic prediction ferroptosis-related genes (FRGs) remains elusive.The mRNA expression profiles gene variation corresponding clinical data NON-TUMOR control were downloaded from public databases. Risk score based on FRGs signature was constructed REMBRANDT cohort validated other datasets including CGGA-693, CGGA-325, TCGA.Our results demonstrated that majority differentially expressed among GBM, LGG, groups (96.6%). Furthermore, with low-risk exhibited more satisfactory outcome. The better also no matter grade they affiliated. Functional analysis revealed high-risk group positively correlated enrichment scores immune checkpoint blockade-related positive signatures, indicating critical role immunotherapy via risk score.A novel FRGs-related predict patients.

Язык: Английский

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Neoadjuvant immunotherapy, chemotherapy, and combination therapy in muscle-invasive bladder cancer: A multi-center real-world retrospective study

Cell Reports Medicine, Год журнала: 2022, Номер 3(11), С. 100785 - 100785

Опубликована: Окт. 19, 2022

To parallelly compare the efficacy of neoadjuvant immunotherapy (tislelizumab), chemotherapy (gemcitabine and cisplatin), combination therapy (tislelizumab + GC) in patients with muscle-invasive bladder cancer (MIBC) explore predictors, we perform a multi-center, real-world cohort study that enrolls 253 treated treatments (combination therapy: 98, chemotherapy: 107, immunotherapy: 48) from 15 tertiary hospitals. We demonstrate achieves highest complete response rate pathological downstaging compared or chemotherapy. develop validate an prediction model consisting pretreatment clinical characteristics, which can pinpoint candidates to receive therapy. also preliminarily reveal who achieve after plus maximal transurethral resection tumor may be safe preservation Overall, this highlights benefit based on tislelizumab for MIBC.

Язык: Английский

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CD8+ T effector and immune checkpoint signatures predict prognosis and responsiveness to immunotherapy in bladder cancer

Oncogene, Год журнала: 2021, Номер 40(43), С. 6223 - 6234

Опубликована: Сен. 22, 2021

Язык: Английский

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