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
Format: Article
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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Summary: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.
ISSN:1471-2407