逆向工程FLT3-PI3K/AKT轴以增强肿瘤浸润淋巴细胞功能并改善卵巢癌和宫颈癌的预后。

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

作者信息

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

机构信息

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.

Department of Cervical, Xiamen Women and Children's Healthcare Hospital, Women's and Children's Hospital of Xiamen University, #10 Zhenhai Road, Xiamen, 361000, People's Republic of China.

出版信息

J Ovarian Res. 2025 Jan 25;18(1):14. doi: 10.1186/s13048-025-01592-8.

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.