A highly resolved integrated single-cell atlas of HPV-negative head and neck cancer

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Abstract Head and Neck Squamous Cell Carcinomas (HNSCC) are the seventh most prevalent form of cancer associated with human papilloma virus infection (HPV-positive) or tobacco alcohol use (HPV-negative). HPV-negative HNSCCs have a high recurrence rate, individual patients’ responses to treatment vary greatly due level cellular heterogeneity tumor its microenvironment. Here, we describe HNSCC single cell atlas, which created by integrating six publicly available datasets encompassing over 230,000 cells across 54 patients. We contextualized relationships between existing signatures populations, identified new subpopulations, show power this large-scale resource robustly identify associations transcriptional clinical phenotypes that would not be possible discover using fewer reveal previously undefined myeloid population, sex-associated changes in type proportions, novel interactions CXCL8-positive fibroblasts vascular endothelial cells. Beyond our findings, atlas will serve as public for high-resolution characterization HNSCC.

Language: Английский

Perioperative risk factors for prognosis in patients undergoing radical esophagectomy: A retrospective study

World Journal of Gastrointestinal Surgery, Journal Year: 2025, Volume and Issue: 17(4)

Published: March 29, 2025

BACKGROUND Esophageal cancer constitutes one of the most aggressive malignant neoplasms associated with poor clinical outcomes. While surgical resection remains cornerstone curative intervention, optimization perioperative care protocols has emerged as an essential strategy to reduce postoperative complications and potentially improve long-term survival rates in patients undergoing esophagectomy. However, substantial debate persists regarding relative importance various risk factors their impact on post-resection AIM To identify affecting prognosis after radical esophagectomy, aiming patient outcomes through targeted interventions. METHODS A retrospective study analyzed 378 esophageal who underwent esophagectomy (McKeown, Sweet, or Ivor-Lewis procedures) from January 2022 December 2023. All operations were performed by experienced surgeons following standardized protocols. The investigation gathered data demographics, parameters, tumor pathology (using 8th edition American Joint Committee Cancer staging system), Statistical analyses utilized Kaplan-Meier estimates Cox proportional hazards modeling, adjustment for confounding variables. RESULTS Multivariate analysis identified three independent predictors survival: Tumor-node-metastasis [Hazard ratio (HR) = 2.31, 95% confidence interval (CI): 1.72-3.10, P < 0.001], differentiation (moderate: HR 1.46, 95%CI: 1.02-2.09, 0.038; poor: 2.15, 1.47-3.14, 0.001), extended analgesic use (> 5 days) (HR 1.43, 1.08-1.89, 0.012). demonstrated significantly lower overall requiring analgesics > days compared ≤ (P 0.003), consistent patterns observed both opioid 0.019) nonsteroidal anti-inflammatory drug 0.028). group exhibited a higher proportion elderly (48.47% vs 35.57%, 0.015), while other baseline characteristics features remained comparable between groups. CONCLUSION staging, differentiation, duration independently predict underscoring significance optimal pain management

Language: Английский

Neuritin-specific antibody impedes the Treg-mediated suppression of anti-tumor immunity and enhances response to anti-PD1

Molecular Immunology, Journal Year: 2025, Volume and Issue: 181, P. 148 - 159

Published: March 29, 2025

Regulatory T cells (Tregs) and effector play critical roles in tumor immunity, with Tregs suppressing immune responses contributing to an immunosuppressive microenvironment (TME). Neuritin-1 (Nrn), a neuropeptide, has been identified enhance Treg expansion. However, its role cell biology development remains unclear. We demonstrated that Nrn is highly expressed the in-vitro-induced (iTregs). Functionally, promoted iTreg differentiation dose-dependent manner, while deletion or anti-Nrn antibody treatment significantly inhibited differentiation. Additionally, suppressed IL-2 transcription secretion cells, impairing activation pro-inflammatory cytokine production. Treg-specific knockout mice exhibited reduced B16 melanoma growth, decreased infiltration, increased infiltration. Conversely, overexpression of accelerated progression by enhancing Treg-mediated suppression. Importantly, we developed first antibody, which effectively tumour enhanced T-cell activity. synergistically worked anti-PD1 improved response reducing increasing function tumor-infiltrated resulting regression. Our findings identify as regulator suppression, progression. Targeting alone combined therapy represents promising strategy anti-tumor immunity.

Language: Английский