A multi-omics approach to reveal critical mechanisms of activator protein 1 (AP-1)

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117225 - 117225

Published: July 30, 2024

The Activator Protein 1 (AP-1) transcription factor complex plays a pivotal role in the regulation of cancer-related genes, influencing cancer cell proliferation, invasion, migration, angiogenesis, and apoptosis. Composed multiple subunits, AP-1 has diverse roles across different types environmental contexts, but its specific mechanisms remain unclear. advent multi-omics approaches shed light on more comprehensive understanding AP-1's mechanism gene regulation. This review collates recent genome-wide data provides an overview expression, structure, function, interaction diseases. An examination these findings can illuminate intricate nature significant involvement progression Moreover, we discuss potential use as target for individual therapy explore various challenges associated with such approach. Ultimately, this valuable insights into biology therapeutic disease treatments.

Language: Английский

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Re‐evaluating prognostic indicators: The critical role of body composition and gene expression in endometrial cancer outcomes

International Journal of Gynecology & Obstetrics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

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Society for Immunotherapy of Cancer (SITC) consensus statement on essential biomarkers for immunotherapy clinical protocols

Journal for ImmunoTherapy of Cancer, Journal Year: 2025, Volume and Issue: 13(3), P. e010928 - e010928

Published: March 1, 2025

Immunotherapy of cancer is now an essential pillar treatment for patients with many individual tumor types. Novel immune targets and technical advances are driving a rapid exploration new strategies incorporating agents in clinical practice. Immunotherapies perturb complex system interactions among genomically unstable cells, diverse cells within the microenvironment including systemic adaptive innate cells. The drive to develop increasingly effective immunotherapy regimens tempered by risk immune-related adverse events. Evidence-based biomarkers that measure potential therapeutic response and/or toxicity critical guide optimal patient care contextualize results trials. Responding lack guidance on biomarker testing early-phase trials, we propose definition listing recommended inclusion all such protocols. These recommendations based consensus provided Society Cancer (SITC) Clinical Immuno-Oncology Network (SCION) faculty input from SITC Pathology Biomarker Committees Journal ImmunoTherapy readership. A consensus-based selection was conducted using Delphi survey SCION faculty. Regular updates these planned. inaugural list includes complete blood count differential generate neutrophil-to-lymphocyte ratio or immune-inflammation index, serum lactate dehydrogenase albumin, programmed death-ligand 1 immunohistochemistry, microsatellite stability assessment, mutational burden. Inclusion across trials will capture variation provide deeper insight into novel established therapies, support improved stratification later-phase

Language: Английский

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Sex-Related Differences in Immunotherapy Toxicities: Insights into Dimorphic Responses

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1054 - 1054

Published: March 21, 2025

Significant sex-based differences exist in the immune system and antitumor responses, potentially leading to variations both efficacy toxicity of anticancer immunotherapies. Women generally mount stronger innate adaptive responses than men, which can result more severe immune-related adverse events (irAEs) during treatments with checkpoint inhibitors (ICIs). However, importance sex dimorphism safety cancer immunotherapy remains underexplored clinical oncology, despite its profound implications for treatment outcomes. Our review highlights critical influence biological on pharmacokinetics, pharmacodynamics, shaping ICI prevalence, type, severity irAEs. Integrating as a variable trial design is essential personalizing therapeutic strategies, bridging existing knowledge gaps, enhancing survival rates quality life patients across genders.

Language: Английский

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Epigenomic regulation of stemness contributes to the low immunogenicity of the most mutated human cancer

Cell Reports, Journal Year: 2025, Volume and Issue: unknown, P. 115561 - 115561

Published: April 1, 2025

Despite harboring the highest tumor mutational burden of all cancers, basal cell carcinoma (BCC) has low immunogenicity. Here, we demonstrate that BCC's immunogenicity is associated with epigenomic suppression antigen presentation machinery reminiscent its origin. Primary BCC had T infiltrates and human leukocyte class I (HLA-I) expression compared cutaneous squamous (SCC) normal keratinocytes. Forkhead box C1 (Foxc1), a regulator quiescence in hair follicle stem cells, was expressed BCC. Foxc1 bound to promoter interferon regulatory factor 1 HLA-I genes, leading their deacetylation reduced expression. A histone deacetylase inhibitor, entinostat, overcame Foxc1's effect upregulated Topical entinostat plus imiquimod immunotherapy blocked development mice. Collectively, our findings stem-like quiescent program preserved which can be enable immunotherapy.

Language: Английский

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Spatial analysis identifies DC niches as predictors of pembrolizumab therapy in head and neck squamous cell cancer

Cell Reports Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 102100 - 102100

Published: April 1, 2025

Head and neck squamous cell carcinoma (HNSCC) shows variable response to anti-programmed death protein 1 (PD-1) therapy, which can be partially explained by a combined positive score (CPS) of tumor immune expression programmed death-ligand (PD-L1) within the local microenvironment (TME). To better define TME determinants associated with treatment efficacy, we conduct study n = 48 HNSCC tumors from patients prior pembrolizumab therapy. Our investigation combines rapid bioorthogonal multiplex staining method computational analysis whole-slide imaging capture single-cell spatial heterogeneity complexity TME. Analyzing 6,316 fields view (FOVs), provide comprehensive PD-L1 phenotyping proximity assays across entirety tissue sections. While none metrics adequately predict response, find that organization CCR7+ dendritic cells (DCs) in niches predicts overall patient survival than CPS alone. This highlights importance understanding context networks for immunotherapy.

Language: Английский

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Precision Targeting in Metastatic Prostate Cancer: Molecular Insights to Therapeutic Frontiers

Biomolecules, Journal Year: 2025, Volume and Issue: 15(5), P. 625 - 625

Published: April 27, 2025

Metastatic prostate cancer (mPCa) remains a significant cause of cancer-related mortality in men. Advances molecular profiling have demonstrated that the androgen receptor (AR) axis, DNA damage repair pathways, and PI3K/AKT/mTOR pathway are critical drivers disease progression therapeutic resistance. Despite established benefits hormone therapy, chemotherapy, bone-targeting agents, mPCa commonly becomes treatment-resistant. Recent breakthroughs highlighted importance identifying actionable genetic alterations, such as BRCA2 or ATM defects, render tumors sensitive to poly-ADP ribose polymerase (PARP) inhibitors. Parallel efforts refined imaging—particularly prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography—to detect localize metastatic lesions with high sensitivity, thereby guiding patient selection for PSMA-targeted radioligand therapies. Multi-omics innovations, including liquid biopsy technologies, enable real-time tracking emergent AR splice variants reversion mutations, supporting adaptive therapy paradigms. Nonetheless, complexity necessitates combination strategies, pairing inhibition PI3K/AKT blockade PARP inhibitors, inhibit tumor plasticity. Immuno-oncological approaches remain challenging unselected patients; however, subsets mismatch deficiency neuroendocrine phenotypes may benefit from immune checkpoint targeted epigenetic interventions. We present these pivotal advances, discuss how biomarker-guided integrative treatments can improve management.

Language: Английский

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Distribution of Inflammatory Infiltrate in Feline Mammary Lesions: Relationship With Clinicopathological Features

Veterinary and Comparative Oncology, Journal Year: 2024, Volume and Issue: 22(3), P. 398 - 409

Published: June 11, 2024

ABSTRACT Inflammation is a frequent finding in feline mammary neoplasms. Recent research suggests that the presence and location of tumour‐associated immune cells might play significant role clinical outcome carcinomas. The present study aimed to characterise overall inflammatory infiltrates healthy, hyperplastic/dysplastic, benign malignant lesions gland, evaluate its association with clinicopathological features. Perilesional intralesional foci were evaluated 307 from 185 queens, categorised according distribution intensity. presence, density tertiary lymphoid structures also assessed. A control group included 24 queens without changes. perilesional infiltrate was observed majority (80.8% 90.2%, respectively), but differed type lesion, being more remarkable Only scarce individual 28.1% normal glands. Data analysis revealed statistically associations ( p < 0.05) between prominent reaction several features associated worse prognosis, including stage, tumour size, mitotic count, lymphovascular invasion lymph node metastasis. Furthermore, significantly tumours an infiltrative growth According our results, different types development aggressive tumours.

Language: Английский

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In Silico–Designed TGFβRI/TGFβRII Receptor Complex Peptide Inhibitors Exhibit Biological Activity In Vitro

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(8)

Published: April 1, 2025

ABSTRACT TGF‐β (transforming growth factor β) is a pleiotropic cytokine found in three isoforms humans. It regulates cell proliferation, wound healing, immune recruitment, contributes to epithelial‐to‐mesenchymal transition (EMT) and the conversion of fibroblasts myofibroblasts. signalling pathway hyperactivity underlies many human disorders. The aim this study was evaluate series novel, silico–designed peptide inhibitors (PIs) TGFβ/TGFβRI/TGFβRII complex. Luciferase‐based luminescence assays on HEK293T cells were used comparatively assess PI biological activity calculate IC 50 values. Flow cytometry cytotoxicity cells. PIs caused significant level reductions compared controls. Additionally, that did not differ significantly from effects SD‐208, small molecule TGFβ inhibitor. None exhibited cytotoxicity. Our TGFBR have demonstrated vitro, with no observed results suggest may be interest treatment fibrotic disorders, chronic inflammatory diseases, or certain neoplastic cancers. will further refined silico tested via carried out cancer lines CD4+/CD8+ T

Language: Английский

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HGH1 and the immune landscape: a novel prognostic marker for immune-desert tumor microenvironment identification and immunotherapy outcome prediction in human cancers

Cell Cycle, Journal Year: 2023, Volume and Issue: 22(18), P. 1969 - 1985

Published: Sept. 17, 2023

HGH1 homolog, a protein-coding gene, plays crucial role in human growth and development. However, its cancer remains unclear. For the first time, this study comprehensively evaluated potential involvement of prognosis immunological function. To achieve this, data from various databases, including The Cancer Genome Atlas, Genotype Tissue Expression, Cell Lineage Encyclopedia, Human Protein cBioPortal, Tumor Immune Estimation Resource Abundance Identifier, were collated, as well one large clinical study, three immunotherapy cohorts vitro experiments. This aims to elucidate expression immune response. Our findings revealed significant association between increased worse across types. Predominantly, copy number variations identified most common genetic mutations. Additionally, was observed not only regulate cell cycle-related functions promote proliferation but also influence autoimmunity-related within both innate adaptive systems, along with other relevant immune-related signaling pathways. Gene set enrichment analysis gene variation used substantiate these findings. overexpression contributed an immune-deficient (immune-desert) tumor microenvironment, which characterized by features such pathway immune-infiltrating cells. Furthermore, correlation mutational burden four cancers microsatellite instability eight observed. suggests that has immunotherapeutic target. Immunotherapy supports notion, demonstrating patients low treated checkpoint inhibitors exhibit improved survival rates higher likelihood responding than high expression. Collectively, highlight cancers, illuminating tumorigenesis immunity. Elevated be indicative immune-desert microenvironment. Consequently, targeting HGH1, particularly combination inhibitor therapy, holds promise for enhancing therapeutic outcomes cancer.

Language: Английский

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