FOXP3 as a prognostic marker and therapeutic target in immunogenic cell death modulation for clear cell renal cell carcinoma

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 30, 2025

Abstract Background Clear cell renal carcinoma (ccRCC) remains a challenging cancer type due to its resistance standard treatments. Immunogenic death (ICD) has the potential activate anti-tumor immunity, presenting promising avenue for ccRCC therapies. Methods We analyzed data from GSE29609, TCGA-KIRC, and GSE159115 identify ICD-related prognostic genes in ccRCC. By applying consensus clustering, patients were categorized based on ICD modification patterns, an signature (ICDS) model was developed using PCA approach. Functional studies conducted with FOXP3 knockdown lines explore impact behavior. Results Eleven identified as key indicators ccRCC, high ICDS linked worse survival outcomes. High also correlated increased levels of immune-suppressive cells within tumor microenvironment. highlighted critical gene influencing ICD, where significantly reduced proliferation migration, underscoring role progression. Conclusions This study establishes pivotal factor regulation Targeting other pathways could enhance treatment efficacy providing foundation ICD-based therapeutic strategies. Evaluating patterns may guide patient-specific interventions, paving way improved management this aggressive cancer.

Language: Английский

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PROGNOSTIC SIGNIFICANCE OF FOXP3 IN RADICALLY TREATED NON-SMALL CELL LUNG CANCER PATIENTS

Art of Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 25 - 32

Published: April 2, 2025

Regulatory T-cells (Tregs), which are characterized by the expression of transcription factor Forkhead box P3 (Foxp3), play a crucial role in modulating immune response. While Tregs primarily recognized for their immunosuppressive functions, influence on survival and prognosis patients with non-small cell lung cancer (NSCLC) presents complex often variable picture. This variability can manifest range outcomes, influencing patient positive, negative, or neutral ways. Our study aims to delve into prognostic significance Foxp3 undergoing radical treatment NSCLC, seeking relationship between Treg dynamics outcomes. involved cohort forty-two diagnosed at stages IA IIIB, all whom underwent surgical intervention followed an adjuvant regimen platinum-based chemotherapy. The inclusion criteria were: who had previously received neoadjuvant chemotherapy radiation therapy. Those experienced postoperative complications, individuals significant concurrent health conditions were systematically excluded from participation. Comprehensive clinicopathological data each extracted medical records ensure accuracy reliability. To evaluate presence FOXP3-positive cells, we employed immunohistochemistry techniques established threshold 23 cells per 1 mm². Patients subsequently stratified two distinct groups based FOXP3 levels: low group (<23 cells/1 mm²) high (≥23 mm²). We compared clinical outcomes these ascertain any differences. A statistical analysis utilizing Mann-Whitney test, Chi-squared receiver operating characteristic (ROC) analysis, Kaplan-Meier method Log-rank test comprehensively data. density Foxp3-positive lymphocytes within tumor microenvironment exhibited notable variability, ranging 5 as many 72 square millimeter. Interestingly, revealed no associations levels selected features patients. Moreover, comparative evaluation showed marked differences adenocarcinomas squamous carcinomas respect characteristics examined. Importantly, versus did not demonstrate disparities recurrence-free overall survival, indicated log-rank p-values 0.1817 0.3944, respectively. However, discernible trend emerged, suggesting that exhibiting lower tended experience improved RFS OS Research indicates both survival. Furthermore, lack correlation associated has been observed. may discrepancies noted

Language: Английский

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The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 9, 2024

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through regulation protein degradation function. By influencing expression checkpoint-associated proteins, UPS modulates T cell-mediated anti-tumor responses can potentially facilitate escape tumor cells. Additionally, contributes to remodeling immunosuppressive microenvironment (TIME) by regulating B cells, dendritic (DCs), macrophages, Treg Targeting conjunction with combining these other therapeutic approaches, may significantly enhance efficacy combination therapies pave way for novel cancer treatment strategies. In this review, we first summarize composition alterations TIME, particular emphasis on TIME its interactions various cell types. Finally, explore potential UPS-targeted immunotherapy substantially improve effectiveness patient survival outcomes.

Language: Английский

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Integrating machine learning, bioinformatics and experimental verification to identify a novel prognostic marker associated with tumor immune microenvironment in head and neck squamous carcinoma

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Dec. 10, 2024

Head and neck squamous carcinoma (HNSC), characterized by a high degree of malignancy, develops in close association with the tumor immune microenvironment (TIME). Therefore, identifying effective targets related to HNSC TIME is paramount importance. Here, we employed ESTIMATE algorithm compute stromal cell scores for samples from TCGA database identified differentially expressed genes (DEGs) based on these scores. Subsequently, utilized four machine learning algorithms identify key genes: ITM2A, FOXP3, WIPF1, RSPO1 DEGs. Through comprehensive pan-cancer analysis, our study aberrant expression ITM2A across various types, significant TIME. Specifically, was markedly reduced correlated poor prognosis HNSC. Functional enrichment analysis revealed that implicated multiple immune-related pathways, including immune-infiltrating cells, checkpoints, immunotherapeutic responses. observed populations through single-cell analysis. Furthermore, showed overexpression inhibited growth cells. Our results suggest may be novel prognostic marker associated

Language: Английский

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