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逆向工程 FLT3-PI3K/AKT 轴以增强 TIL 功能并改善卵巢癌和宫颈癌的预后

英文原题:Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.

PubMed 2025/01/25(内容时间) J Ovarian Res Q1 · IF 5.3(JCR 2025)

研究概要

本研究首次提供了FLT3在OC和CC中免疫调节作用的空间分辨证据,将其定位为一个有前景的免疫治疗靶点。靶向FLT3的策略可能为对常规治疗耐药的患者提供新选择。

研究思路结论见上方概要

卵巢癌(OC)和宫颈癌(CC)的生存率较低。TIL(肿瘤浸润淋巴细胞)(TILs)在预后中起关键作用,但共享的免疫机制仍不明确。

我们整合了scRNA-seq和ST,以探究OC和CC中的免疫调节,重点关注PI3K/AKT通路和FLT3作为关键调节因子。采用Seurat和Harmony进行批次校正和降维。利用10 × Genomics的空间数据对FLT3表达进行了定位。

FLT3 通过 PI3K/AKT 通路被鉴定为一个调节因子,与 T 细胞、NK 细胞和 B 细胞呈正相关。FLT3 高表达区域表现出免疫浸润增加,尤其是在 CC 中,从而改善了生存结局。

展开英文摘要原文

BACKGROUND: Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive. METHODS: We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators. Seurat and Harmony were employed for batch correction and dimensionality reduction. FLT3 expression was mapped with spatial data from 10 × Genomics. RESULTS: FLT3, identified as a regulator through the PI3K/AKT pathway, showed positive correlations with T cells, NK cells, and B cells. FLT3-high regions exhibited increased immune infiltration, particularly in CC, enhancing survival outcomes. CONCLUSION: This study provides the first spatially resolved evidence of FLT3's immune-modulatory role in OC and CC, positioning it as a promising immunotherapeutic target. FLT3-targeted strategies may offer new options for patients resistant to conventional therapies.

论文信息

作者
Hao F、Yan Z、Shen L、Hui W、Ling Q、Xiaoyu Y、Hua J
第一作者单位
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.China
通讯作者单位
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China. jianghua@fudan.edu.cn.China
期刊
Journal of ovarian research2025 Jan 25
原文标识
PubMed 39863894 · DOI 10.1186/s13048-025-01592-8