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

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

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.

Keywords: Cervical cancer; FLT3; Ovarian cancer; PI3K/AKT pathway; Spatial transcriptomics; Tumor-infiltrating lymphocytes (TILs).

MeSH terms

  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Lymphocytes, Tumor-Infiltrating* / metabolism
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / immunology
  • Ovarian Neoplasms* / mortality
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / immunology
  • Uterine Cervical Neoplasms* / mortality
  • fms-Like Tyrosine Kinase 3* / genetics
  • fms-Like Tyrosine Kinase 3* / metabolism

Substances

  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • fms-Like Tyrosine Kinase 3
  • FLT3 protein, human