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

IF 4.2 3区医学 Q1 REPRODUCTIVE BIOLOGY Journal of Ovarian Research Pub Date : 2025-01-25 DOI:10.1186/s13048-025-01592-8

Feng Hao, Zhang Yan, Luo Shen, Wang Hui, Qiu Ling, Yang Xiaoyu, Jiang Hua

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Abstract

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.

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对FLT3-PI3K/AKT轴进行逆向工程以增强TILs功能并改善卵巢癌和宫颈癌的预后

背景：卵巢癌（OC）和宫颈癌（CC）的生存率较低。肿瘤浸润淋巴细胞（til）在预后中起关键作用，但共同的免疫机制仍不清楚。方法：结合单细胞RNA测序（scRNA-seq）和空间转录组学（ST）方法，研究OC和CC的免疫调控，重点研究PI3K/AKT通路和FLT3作为关键调节因子。采用Seurat和Harmony进行批量校正和降维。利用10 × Genomics的空间数据绘制FLT3表达图谱。结果：FLT3通过PI3K/AKT通路被鉴定为调节因子，与T细胞、NK细胞和B细胞呈正相关。flt3高区表现出免疫浸润增加，特别是在CC中，提高了生存结果。结论：本研究首次提供了FLT3在OC和CC中免疫调节作用的空间证据，将其定位为有前景的免疫治疗靶点。针对flt3的策略可能为对常规治疗有耐药性的患者提供新的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Ovarian Research REPRODUCTIVE BIOLOGY-

CiteScore

6.20

自引率

2.50%

发文量

125

审稿时长

>12 weeks

期刊介绍： Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.