Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers
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 (...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Journal of Ovarian Research |
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| Online Access: | https://doi.org/10.1186/s13048-025-01592-8 |
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| author | Feng Hao Zhang Yan Luo Shen Wang Hui Qiu Ling Yang Xiaoyu Jiang Hua |
| author_facet | Feng Hao Zhang Yan Luo Shen Wang Hui Qiu Ling Yang Xiaoyu Jiang Hua |
| author_sort | Feng Hao |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3b2079b5ffa94a53a46d9b8a79eb2952 |
| institution | Kabale University |
| issn | 1757-2215 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj-art-3b2079b5ffa94a53a46d9b8a79eb29522025-01-26T12:47:44ZengBMCJournal of Ovarian Research1757-22152025-01-0118111910.1186/s13048-025-01592-8Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancersFeng Hao0Zhang Yan1Luo Shen2Wang Hui3Qiu Ling4Yang Xiaoyu5Jiang Hua6Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Cervical, Xiamen Women and Children’s Healthcare Hospital, Women’s and Children’s Hospital of Xiamen UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityHK International Regenerative CentreDepartment of Gynecology, Obstetrics and Gynecology Hospital of Fudan UniversityAbstract 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.https://doi.org/10.1186/s13048-025-01592-8FLT3PI3K/AKT pathwayTumor-infiltrating lymphocytes (TILs)Ovarian cancerCervical cancerSpatial transcriptomics |
| spellingShingle | Feng Hao Zhang Yan Luo Shen Wang Hui Qiu Ling Yang Xiaoyu Jiang Hua Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers Journal of Ovarian Research FLT3 PI3K/AKT pathway Tumor-infiltrating lymphocytes (TILs) Ovarian cancer Cervical cancer Spatial transcriptomics |
| title | Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers |
| title_full | Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers |
| title_fullStr | Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers |
| title_full_unstemmed | Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers |
| title_short | Reverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers |
| title_sort | reverse engineering the flt3 pi3k akt axis to enhance tils function and improve prognosis in ovarian and cervical cancers |
| topic | FLT3 PI3K/AKT pathway Tumor-infiltrating lymphocytes (TILs) Ovarian cancer Cervical cancer Spatial transcriptomics |
| url | https://doi.org/10.1186/s13048-025-01592-8 |
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