NAD⁺ Metabolism Reprogramming Drives SIRT1‐Dependent Deacetylation Inducing PD‐L1 Nuclear Localization in Cervical Cancer

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 23, 2025

Abstract Cervical cancer (CC) is a major health threat to women, with immunotherapies targeting the programmed death receptor 1/programmed ligand 1(PD‐1/PD‐L1) axis showing promise but encountering resistance in significant patient population. This has driven critical quest uncover underlying mechanisms. study uncovers novel metabolic involving nicotinamide adenine dinucleotide (NAD + ) salvage pathway enzyme phosphoribosyltransferase (NAMPT) and deacetylase Sirtuin 1 (SIRT1), which regulates PD‐L1 expression nuclear localization CC. may be key factor contributing observed immunotherapy. reveals that overexpression cancers regulated by both transcriptional post‐transcriptional processes. Acetyl‐proteomic analysis pinpoints SIRT1 as central regulator deacetylation of histone H3 at lysines 27, influence subcellular distribution. finding epigenetic control immune checkpoint proteins pathways, offering new perspective on regulation PD‐L1. The identification NAMPT/SIRT1 suggests this enhance therapeutic responses.

Язык: Английский

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Prediction of pathological complete response to neoadjuvant chemoimmunotherapy in non–small cell lung cancer using 18F-FDG PET radiomics features of primary tumour and lymph nodes

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Март 21, 2025

Predicting the response to neoadjuvant chemoimmunotherapy in patients with resectable non-small cell lung cancer (NSCLC) facilitates clinical treatment decisions. Our study aimed establish a machine learning model that accurately predicts pathological complete (pCR) using 18F-FDG PET radiomics features. We retrospectively included 210 NSCLC who completed and subsequently underwent surgery results, categorising them into training set of 147 test 63 patients. Radiomic features were extracted from primary tumour lymph nodes. Using 10-fold cross-validation least absolute shrinkage selection operator method, we identified most impactful radiomic The screened univariate multivariate analyses. Machine models developed random forest leading establishment one feature model, two fusion models. performance these was evaluated based on area under curve (AUC). In set, three showed comparable AUC values, ranging 0.901 0.925. underperformed, an 0.677. Fusion_LN1LN2 achieved highest (0.823), closely followed by Fusion_Lnall 0.729. moderate 0.666, whereas had lowest at 0.631. Additionally, demonstrated positive net reclassification improvement integrated discrimination values compared other models, employed SHapley Additive exPlanations methodology interpret results our optimal model. 18F-FDG-PET, will assist clinicians predicting pCR before for NSCLC.

Язык: Английский

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Single-cell and spatial transcriptomic analyses revealing tumor microenvironment remodeling after neoadjuvant chemoimmunotherapy in non-small cell lung cancer

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Апрель 9, 2025

Non-small cell lung cancer (NSCLC) represents the most common pathological type of cancer, and combination neoadjuvant immunotherapy with chemotherapy has emerged as first-line treatment for NSCLC. Nevertheless, efficacy this therapeutic approach remains variable. The present study aims to examine impact chemoimmunotherapy in NSCLC patients, a view identifying key molecules, critical subpopulations, communication patterns spatial distributions that potentially correlate sensitivity. A total 16 tissue samples were collected from cohort 12 patients subjected single-cell RNA transcriptome sequencing. Our data demonstrated distribution CD4 + Treg T cells mCAFs indicated an immunosuppressive tumor microenvironment, while accumulation Th17 iCAFs could act positive marker sensitivity chemoimmunotherapy. Furthermore, significant high level SELENOP-macrophages was observed tissues responders, strong co-localization between antigen-presenting associated fibroblasts (CAFs) boundaries identified, indicating cooperative roles these two types response combined therapy. Moreover, be accumulated tertiary lymphoid structures, which further suggested its role recruiting lymphocytes. analysis cell-cell communication, based on transcriptomics, suggests interactions SELENOP-macrophages, apCAFs, CD8 significantly enhanced responders. In addition, recruited Naïve, Helper Naïve through pathways such cholesterol, interleukin, chemokine HLA when responding unveils dynamic transcriptional changes microenvironment non-small

Язык: Английский

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The Lung Cancer Immune Prognostic Score predicts pathologic complete response and survival in NSCLC patients receiving neoadjuvant immunochemotherapy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 16, 2025

Introduction Neoadjuvant immunochemotherapy (nICT) has significantly improved event-free survival (EFS) and pathologic complete response (pCR) in patients with resectable non-small cell lung cancer (NSCLC). However, the lack of validated biomarkers limits their ability to predict therapeutic efficacy outcomes. This study aimed develop a novel inflammatory nutritional index, Lung Cancer Immune Prognostic Score (LCIPS), pCR prognosis NSCLC. Methods retrospective included 131 clinical stage IB-IIIB NSCLC who underwent neoadjuvant between May 2020 2024. Baseline data hematological parameters were collected. Lasso regression analysis was employed identify indices associated pCR, LCIPS constructed based on these factors. Kaplan-Meier log-rank tests used assess differences. Logistic performed predictors while Cox determined independent prognostic factors for disease-free (DFS) overall (OS). The predictive performance using nomogram. Results identified three core indices: albumin-to-globulin ratio (A/G), absolute monocyte count (MONO), lymphocyte (LYM). formula as follows: LCIPS=0.900×A/G+0.761×MONO (10 9 /L) −0.065×LYM /L). Receiver operating characteristic (ROC) curve showed that had superior (area under (AUC) = 0.68) compared other classical markers. Univariate multivariate logistic analyses intraoperative lymph node dissection status A/G ( p < 0.05). Multivariate demonstrated smoking DFS OS. Nomogram validation indicated robust accuracy LCIPS. Notably, among immune-related adverse events (irAEs), endocrine- cardiac-related irAEs affected Discussion is an predictor receiving index offers valuable guidance personalized treatment strategies.

Язык: Английский

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Does high PD-L1 expression reduce the risk of relapse after definitive surgery in patients with oral cavity cancer?

Acta Oto-Laryngologica, Год журнала: 2025, Номер unknown, С. 1 - 6

Опубликована: Апрель 23, 2025

Uncovering the molecular mechanisms of cancer pathogenesis is crucial for improving survival outcomes. This study investigates impact programmed death ligand 1 (PD-L1) expression on risk progression in patients with oral squamous cell carcinoma (OSCC). The retrospective included adult diagnosed OSCC between January 2012 and December 2023. PD-L1 tissue removed by definitive surgery was evaluated using immunohistochemistry, tumor proportion score (TPS) combined positive (CPS) were calculated. Survival analyses performed to assess its prognostic implications. Among 96 patients, TPS CPS 20% or above 52 (54.2%) 65 (67.7%) cases, respectively. ≥20% associated mucosal lip location, earlier disease stage, decreased progression. multivariate Cox regression model revealed that stage III/IV (HR: 2.176, 95%CI: 1.085-4.376, p = .029) 0.241, 0.066-0.879, .031) independent factors progression-free survival. increased tumoral may reduce OSCC. These findings underscore potential significance following surgical resection.

Язык: Английский

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Progress on neoadjuvant immunotherapy in resectable non-small cell lung cancer and potential biomarkers

Frontiers in Oncology, Год журнала: 2023, Номер 12

Опубликована: Янв. 24, 2023

Immune checkpoint inhibitors (ICIs) are highly concerned in the treatment of non-small cell lung cancer (NSCLC), represented by programmed death protein 1 (PD-1) and its ligand (PD-L1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). The introduction immunotherapy perioperative NSCLC has improved prognosis to a great extent, as demonstrated several phase II III clinical trials. target population for early-stage is still under discussion, biomarkers neoadjuvant selection next pending problem. predictive efficacy many potential makers being explored, including PD-L1 expression levels, tumor mutation burden, circulating DNA, components microenvironment, factors. We summarize key findings on utility ICIs trials preoperative patients conclude analyses relevant provide better understanding potentially immunotherapy.

Язык: Английский

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Is neoadjuvant immunotherapy necessary in patients with programmed death ligand 1 expression-negative resectable non-small cell lung cancer? A systematic review and meta-analysis

Lung Cancer, Год журнала: 2024, Номер 191, С. 107799 - 107799

Опубликована: Апрель 23, 2024

Язык: Английский

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PD-L1 aptamer-functionalized degradable hafnium oxide nanoparticles for near infrared-II diagnostic imaging and radiosensitization

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Июнь 7, 2023

Immune checkpoint blockade is now recognized as a paradigm-shifting cancer therapeutic strategy, whereas there remains difficulty in accurately predicting immunotherapy efficacy by PD-L1 expression. In addition, radiotherapy for patients faces the problem of insufficient dose at tumor site while which have been not tolerated normal tissues. this study, we created aptamer-anchored spherical nucleic acids (SNAs) with shell made aptamer and indocyanine green (ICG) embedded mesoporous hafnium oxide nanoparticle core (Hf@ICG-Apt). Upon low pH irradiation sites, nano-system enabled release ICG high expression to develop tumor-to-background ratio 7.97 ± 0.76 enhanced retention more than 48 h. Moreover, Hf@ICG-Apt improved radiation therapy (RT) when combined radiation. Notably, showed scarcely any systemic toxicity vivo . Overall, research offered novel approach applying reliable monitoring localization robust RT sensitization against good biosafety.

Язык: Английский

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Identification of a cuproptosis and copper metabolism gene–related lncRNAs prognostic signature associated with clinical and immunological characteristics of hepatocellular carcinoma

Frontiers in Oncology, Год журнала: 2023, Номер 13

Опубликована: Март 28, 2023

The relationship between cuproptosis and HCC is still in the exploratory stage. Long noncoding RNAs (lncRNAs) have recently been linked to progression of hepatocellular carcinoma (HCC). However, clinical significance lncRNAs associated with remains unclear.Based on Cancer Genome Atlas (TCGA) liver (LIHC) dataset, we identified characteristic prognostic by univariate, LASSO, multifactorial regression analysis, constructed a signature cuproptosis-related HCC. role were through CCK-8, clone formation Huh-7 cells high expression FDX1. Prognostic potential was evaluated each two cohorts created randomly dividing TCGA cohort into training test 1:1 ratio. Immune profiles defined subgroups lncRNA features as well drug sensitivity analyzed.We multigene based four (AL590705.3, LINC02870, KDM4A-AS1, MKLN1-AS). These participated development cuproptosis. patients classified high-risk low-risk groups median value risk score. receiver operating curve area under values for 1-, 3-, 5-year survival 0.773, 0.728, 0.647, respectively, cohort, 0.764, 0.671, 0.662, cohort. Univariate analyses indicated that this feature an independent factor Principal component analysis plots clearly distinguished low- terms their probability survival. Furthermore, gene set enrichment showed variety processes tumor proliferation enriched group compared group. Moreover, there significant differences immune cell subpopulations, checkpoint genes, screening, which provided distinct therapeutic recommendations individuals various risks.We novel cuproptosis-associated predictive prognosis Cuproptosis-associated are microenvironment even efficacy immunotherapy.

Язык: Английский

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Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Авг. 3, 2023

The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel combination therapy regimens incorporating further enhance the proportion patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous trials incorporated SBRT into advanced NSCLC, revealing this effectively inhibits growth while simultaneously activating Consequently, integration with emerged as a strategy treating can response eradicate micrometastases recurrent foci post-resection. This review aims elucidate potential mechanism followed by surgery identify optimal treatment strategies. Initially, we delineate interplay between microenvironment, well response. We subsequently introduce preclinical foundation combined NSCLC. Finally, discussed dosage, schedule, biomarkers in its application. In conclusion, elucidation offers theoretical basis ongoing contributes determining most efficacious scheme future

Язык: Английский

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