Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer

Abstract Background Gamma-delta (γδ) T cells are a critical component of the tumor microenvironment and have been recognized as a promising biomarker and target for cancer therapy. Increasing evidence suggests that γδT cells play distinct roles in different cancers. However, the impact of γδT cells...

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Main Authors: Guixin Wang, Shuo Wang, Wenbin Song, Chenglu Lu, Zhaohui Chen, Long He, Xiaoning Wang, Yizeng Wang, Cangchang Shi, Zhaoyi Liu, Yue Yu, Xin Wang, Yao Tian, Yingxi Li
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Language:English
Published: BMC 2025-04-01
Series:BMC Cancer
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Online Access:https://doi.org/10.1186/s12885-025-14029-8
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author Guixin Wang
Shuo Wang
Wenbin Song
Chenglu Lu
Zhaohui Chen
Long He
Xiaoning Wang
Yizeng Wang
Cangchang Shi
Zhaoyi Liu
Yue Yu
Xin Wang
Yao Tian
Yingxi Li
author_facet Guixin Wang
Shuo Wang
Wenbin Song
Chenglu Lu
Zhaohui Chen
Long He
Xiaoning Wang
Yizeng Wang
Cangchang Shi
Zhaoyi Liu
Yue Yu
Xin Wang
Yao Tian
Yingxi Li
author_sort Guixin Wang
collection DOAJ
description Abstract Background Gamma-delta (γδ) T cells are a critical component of the tumor microenvironment and have been recognized as a promising biomarker and target for cancer therapy. Increasing evidence suggests that γδT cells play distinct roles in different cancers. However, the impact of γδT cells in breast cancer remains controversial. Methods In this study, we investigated the role of γδT cells in breast cancer using a comprehensive approach, including bulk and single-cell sequencing, radiomics based on magnetic resonance imaging (MRI), genomic data, and immunohistochemistry. Single-cell RNA profiling was used to infer the potential lineage evolution of γδT cells and their interactions with other immune cells. Bulk RNA sequencing was included to uncover the heterogeneity in signaling pathways, as well as radiotherapy and immunotherapy responses, among patients with varying levels of γδT cell abundance. Genomic analysis was used to recognize the critical gene mutations with the infiltration of γδT cells. Immunohistochemistry was performed to validate the prognostic value of γδT cells in breast cancer patients. Lastly, radiomics was used to establish a correlation between the abundance of γδT cells and the features of MRI images. Results The γδT cell infiltration was closely associated with favorable prognosis in triple-negative breast cancer (TNBC) but not in other subtypes of breast cancer. γδT cells may exert antitumor effects through intrinsic lineage evolution or interact with antigen-presenting cells through ligand-receptor pairs. Patients with a high γδT cell abundance may benefit more from chemotherapy or radiotherapy alone than their combination. Additionally, patients with a high γδT cell abundance were more likely to benefit from immunotherapy. Finally, we established a radiomic model based on dynamic contrast-enhanced-MRI, which indicated the potential for estimating the γδT cell abundance for patients with TNBC. Conclusion Our study provides novel insight and a theoretical basis for individualized therapy of patients with TNBC based on γδT cells.
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spelling doaj-art-a2f9fa3d1fc34adfbb1ec8b3639736aa2025-08-20T03:10:07ZengBMCBMC Cancer1471-24072025-04-0125111610.1186/s12885-025-14029-8Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancerGuixin Wang0Shuo Wang1Wenbin Song2Chenglu Lu3Zhaohui Chen4Long He5Xiaoning Wang6Yizeng Wang7Cangchang Shi8Zhaoyi Liu9Yue Yu10Xin Wang11Yao Tian12Yingxi Li13The First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of Pathology, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Tianjin Cancer Institute and Hospital, Tianjin Medical UniversityThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteDepartment of General Surgery, Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin Medical University General Hospital, Tianjin General Surgery InstituteThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityThe First Department of Breast Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical UniversityImmunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical UniversityAbstract Background Gamma-delta (γδ) T cells are a critical component of the tumor microenvironment and have been recognized as a promising biomarker and target for cancer therapy. Increasing evidence suggests that γδT cells play distinct roles in different cancers. However, the impact of γδT cells in breast cancer remains controversial. Methods In this study, we investigated the role of γδT cells in breast cancer using a comprehensive approach, including bulk and single-cell sequencing, radiomics based on magnetic resonance imaging (MRI), genomic data, and immunohistochemistry. Single-cell RNA profiling was used to infer the potential lineage evolution of γδT cells and their interactions with other immune cells. Bulk RNA sequencing was included to uncover the heterogeneity in signaling pathways, as well as radiotherapy and immunotherapy responses, among patients with varying levels of γδT cell abundance. Genomic analysis was used to recognize the critical gene mutations with the infiltration of γδT cells. Immunohistochemistry was performed to validate the prognostic value of γδT cells in breast cancer patients. Lastly, radiomics was used to establish a correlation between the abundance of γδT cells and the features of MRI images. Results The γδT cell infiltration was closely associated with favorable prognosis in triple-negative breast cancer (TNBC) but not in other subtypes of breast cancer. γδT cells may exert antitumor effects through intrinsic lineage evolution or interact with antigen-presenting cells through ligand-receptor pairs. Patients with a high γδT cell abundance may benefit more from chemotherapy or radiotherapy alone than their combination. Additionally, patients with a high γδT cell abundance were more likely to benefit from immunotherapy. Finally, we established a radiomic model based on dynamic contrast-enhanced-MRI, which indicated the potential for estimating the γδT cell abundance for patients with TNBC. Conclusion Our study provides novel insight and a theoretical basis for individualized therapy of patients with TNBC based on γδT cells.https://doi.org/10.1186/s12885-025-14029-8Gamma-delta T cellsTriple-negative breast cancerImmunotherapyTumor microenvironmentRadiomoics
spellingShingle Guixin Wang
Shuo Wang
Wenbin Song
Chenglu Lu
Zhaohui Chen
Long He
Xiaoning Wang
Yizeng Wang
Cangchang Shi
Zhaoyi Liu
Yue Yu
Xin Wang
Yao Tian
Yingxi Li
Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
BMC Cancer
Gamma-delta T cells
Triple-negative breast cancer
Immunotherapy
Tumor microenvironment
Radiomoics
title Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
title_full Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
title_fullStr Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
title_full_unstemmed Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
title_short Integrating multi-omics data reveals the antitumor role and clinical benefits of gamma-delta T cells in triple-negative breast cancer
title_sort integrating multi omics data reveals the antitumor role and clinical benefits of gamma delta t cells in triple negative breast cancer
topic Gamma-delta T cells
Triple-negative breast cancer
Immunotherapy
Tumor microenvironment
Radiomoics
url https://doi.org/10.1186/s12885-025-14029-8
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