SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer

Abstract P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially li...

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Main Authors: Qingyu Huang, Wenhui Yang, Fuhao Wang, Rui Huang, Qian Wang, Xiaohui Li, Tianyu Lei, Shengqin Yue, Wenxue Zou, Qi An, Jinbo Yue, Qinyong Hu, Chao Liu
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Molecular Cancer
Online Access:https://doi.org/10.1186/s12943-025-02244-7
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author Qingyu Huang
Wenhui Yang
Fuhao Wang
Rui Huang
Qian Wang
Xiaohui Li
Tianyu Lei
Shengqin Yue
Wenxue Zou
Qi An
Jinbo Yue
Qinyong Hu
Chao Liu
author_facet Qingyu Huang
Wenhui Yang
Fuhao Wang
Rui Huang
Qian Wang
Xiaohui Li
Tianyu Lei
Shengqin Yue
Wenxue Zou
Qi An
Jinbo Yue
Qinyong Hu
Chao Liu
author_sort Qingyu Huang
collection DOAJ
description Abstract P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients. The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELP high group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways. Notably, this group demonstrated increased infiltration of CD8+ T cells and enhanced expression of chemokine receptors, including ACKR1. Furthermore, our data suggest that SELP+ TECs engage in crosstalk with CD8+ T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy. In conclusion, these findings underscore the pivotal role of SELP+ TEC:CD8+ T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.
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spelling doaj-art-2e97fd98b094457c87fe6dade5606f062025-02-09T12:15:51ZengBMCMolecular Cancer1476-45982025-02-012411710.1186/s12943-025-02244-7SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancerQingyu Huang0Wenhui Yang1Fuhao Wang2Rui Huang3Qian Wang4Xiaohui Li5Tianyu Lei6Shengqin Yue7Wenxue Zou8Qi An9Jinbo Yue10Qinyong Hu11Chao Liu12Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Oncology, Renmin Hospital of Wuhan UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Oncology, Chongqing University Fuling HospitalDepartment of Oncology, Renmin Hospital of Wuhan UniversityDepartment of Medical Oncology, Peking University First HospitalDepartment of Oncology, Renmin Hospital of Wuhan UniversityDepartment of Oncology, Renmin Hospital of Wuhan UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Oncology, Renmin Hospital of Wuhan UniversityDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesAbstract P-selectin (SELP) expression in tumor cells has been implicated in promoting tumor progression and treatment resistance across various cancers. However, our prior study identified SELP expression in a specific subpopulation of endothelial cells within cervical cancer (CC) and potentially linked to anti-cancer immune response. The precise mechanisms by which SELP influences anti-cancer immunity and its involvement in radiotherapy response in CC, however, remain elusive. To address these gaps, this study analyzed tumor tissue samples from 205 CC patients undergoing radiotherapy, scRNA-seq data from 42,159 cells of eight patients, and bulk RNA-sequencing data from 187 radiotherapy-treated patients. The results revealed that elevated SELP expression in tumor endothelial cells (TECs) was significantly correlated with improved survival outcomes in patients treated with radiotherapy. The SELP high group exhibited a prominent enrichment of immune-related pathways, coupled with a diminished enrichment in epithelial cell proliferation and angiogenesis pathways. Notably, this group demonstrated increased infiltration of CD8+ T cells and enhanced expression of chemokine receptors, including ACKR1. Furthermore, our data suggest that SELP+ TECs engage in crosstalk with CD8+ T cells via the ACKR1-CCL5 axis, which is associated with improved radiotherapy efficacy. In conclusion, these findings underscore the pivotal role of SELP+ TEC:CD8+ T cell interactions through the ACKR1-CCL5 pathway in enhancing radiotherapy response in CC. Targeting this crosstalk may offer novel therapeutic strategies to mitigate treatment resistance and improve patient survival.https://doi.org/10.1186/s12943-025-02244-7
spellingShingle Qingyu Huang
Wenhui Yang
Fuhao Wang
Rui Huang
Qian Wang
Xiaohui Li
Tianyu Lei
Shengqin Yue
Wenxue Zou
Qi An
Jinbo Yue
Qinyong Hu
Chao Liu
SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
Molecular Cancer
title SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
title_full SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
title_fullStr SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
title_full_unstemmed SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
title_short SELP+ TEC:CD8+ T cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
title_sort selp tec cd8 t cell crosstalk associates with improved radiotherapy efficacy in cervical cancer
url https://doi.org/10.1186/s12943-025-02244-7
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