整合多组学数据揭示了γδ T细胞在三阴性乳腺癌中的抗肿瘤作用及临床益处。

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

作者信息

Wang Guixin, Wang Shuo, Song Wenbin, Lu Chenglu, Chen Zhaohui, He Long, Wang Xiaoning, Wang Yizeng, Shi Cangchang, Liu Zhaoyi, Yu Yue, Wang Xin, Tian Yao, Li Yingxi

机构信息

The 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 University, Huan-Hu-Xi Road, He-Xi District, Tianjin, 300060, China.

Immunology Department, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Tianjin Medical University, Qixiangtai Road 22, He-Ping District, Tianjin, 300070, China.

出版信息

BMC Cancer. 2025 Apr 7;25(1):623. doi: 10.1186/s12885-025-14029-8.

DOI:10.1186/s12885-025-14029-8

PMID:40197136

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11974128/

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.

摘要

背景

γδ T细胞是肿瘤微环境的关键组成部分，已被公认为一种有前景的生物标志物和癌症治疗靶点。越来越多的证据表明，γδ T细胞在不同癌症中发挥着不同作用。然而，γδ T细胞在乳腺癌中的影响仍存在争议。

方法

在本研究中，我们采用综合方法研究γδ T细胞在乳腺癌中的作用，包括批量和单细胞测序、基于磁共振成像（MRI）的放射组学、基因组数据和免疫组织化学。单细胞RNA分析用于推断γδ T细胞的潜在谱系进化及其与其他免疫细胞的相互作用。纳入批量RNA测序以揭示不同γδ T细胞丰度水平患者在信号通路、放疗和免疫治疗反应方面的异质性。基因组分析用于识别γδ T细胞浸润相关的关键基因突变。进行免疫组织化学以验证γδ T细胞在乳腺癌患者中的预后价值。最后，利用放射组学建立γδ T细胞丰度与MRI图像特征之间的相关性。

结果

γδ T细胞浸润与三阴性乳腺癌（TNBC）的良好预后密切相关，但在其他乳腺癌亚型中并非如此。γδ T细胞可能通过内在谱系进化发挥抗肿瘤作用，或通过配体-受体对与抗原呈递细胞相互作用。γδ T细胞丰度高的患者单独接受化疗或放疗可能比联合治疗受益更多。此外，γδ T细胞丰度高的患者更有可能从免疫治疗中受益。最后，我们基于动态对比增强MRI建立了一个放射组学模型，该模型显示了估计TNBC患者γδ T细胞丰度的潜力。