Current gene therapy · 2026
Foxp3+ Tregs Promote M2 Macrophage Polarization via Sirt1-ERK1/2- STAT3 Pathway in Ovarian Cancer Progression.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Liang Nai, Chen Hui, Yang Yi, Guo Benlong, Xu Zehai, Li Li, Jin Yunfeng
Аннотация
INTRODUCTION: Epithelial Ovarian Cancer (EOC) is a highly aggressive gynecological malignancy with a high mortality rate primarily due to late-stage diagnosis and metastatic dissemination. Regulatory T cells (Tregs) have emerged as critical mediators of immune evasion, yet the role of Foxp3+ Tregs in modulating Tumor-Associated Macrophage (TAM) polarization and the underlying molecular mechanisms in EOC remains unclear.
METHODS: An orthotopic EOC mouse model and in vitro co-culture systems were employed to investigate the effects of Foxp3+ Tregs on TAM polarization. Quantitative Real-Time PCR (qRTPCR), flow cytometry, Western blotting, wound healing, and transwell assays were performed to assess gene expression, immune cell infiltration, and tumor cell migration/invasion. Foxp3 knockdown was achieved using Adeno-Associated Virus (AAV)-mediated delivery to evaluate its effects in vivo.
RESULTS: Foxp3+ Tregs induced macrophage polarization toward the M2 phenotype, characterized by downregulation of M1 markers (IL-1β, iNOS) and upregulation of M2 markers (IL-10, Arg-1). Mechanistically, Foxp3+ Tregs activated the Sirt1-ERK1/2-STAT3 signaling pathway while suppressing NF-κB activity. In vitro, Foxp3+ Tregs enhanced the migratory and invasive capacities of ovarian cancer cells, whereas in vivo Foxp3 knockdown significantly reduced tumor growth and M2 macrophage infiltration.
DISCUSSION: These findings suggest that Foxp3+ Tregs play a pivotal role in shaping the immunosuppressive tumor microenvironment in EOC by promoting M2 macrophage polarization through Sirt1-ERK1/2-STAT3 signaling and NF-κB suppression, ultimately facilitating tumor progression.
CONCLUSION: Foxp3+ Tregs drive immunosuppressive macrophage polarization and ovarian cancer progression, highlighting Foxp3 as a potential therapeutic target for EOC treatment.
METHODS: An orthotopic EOC mouse model and in vitro co-culture systems were employed to investigate the effects of Foxp3+ Tregs on TAM polarization. Quantitative Real-Time PCR (qRTPCR), flow cytometry, Western blotting, wound healing, and transwell assays were performed to assess gene expression, immune cell infiltration, and tumor cell migration/invasion. Foxp3 knockdown was achieved using Adeno-Associated Virus (AAV)-mediated delivery to evaluate its effects in vivo.
RESULTS: Foxp3+ Tregs induced macrophage polarization toward the M2 phenotype, characterized by downregulation of M1 markers (IL-1β, iNOS) and upregulation of M2 markers (IL-10, Arg-1). Mechanistically, Foxp3+ Tregs activated the Sirt1-ERK1/2-STAT3 signaling pathway while suppressing NF-κB activity. In vitro, Foxp3+ Tregs enhanced the migratory and invasive capacities of ovarian cancer cells, whereas in vivo Foxp3 knockdown significantly reduced tumor growth and M2 macrophage infiltration.
DISCUSSION: These findings suggest that Foxp3+ Tregs play a pivotal role in shaping the immunosuppressive tumor microenvironment in EOC by promoting M2 macrophage polarization through Sirt1-ERK1/2-STAT3 signaling and NF-κB suppression, ultimately facilitating tumor progression.
CONCLUSION: Foxp3+ Tregs drive immunosuppressive macrophage polarization and ovarian cancer progression, highlighting Foxp3 as a potential therapeutic target for EOC treatment.