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CXCR6 表达与三阴性乳腺癌的放疗反应和免疫环境相关：实验研究。

CXCR6 expression correlates with radiotherapy response and immune context in triple-negative breast cancer-experimental studies.

机构信息

Department of Radiation Oncology, Fudan University Shanghai Cancer Center.

Shanghai Key Laboratory of Radiation Oncology.

出版信息

Int J Surg. 2024 Aug 1;110(8):4695-4707. doi: 10.1097/JS9.0000000000001546.

DOI:10.1097/JS9.0000000000001546
PMID:39143706
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11325934/
Abstract

BACKGROUND

The chemokine receptor CXCR6 is critical for sustained tumor control mediated by CD8+ cytotoxic T cells (CTLs) in tumors. Previous studies have shown that ionizing radiation induces an inflamed immune contexture by upregulating CXCR6. However, the clinical significance of CXCR6 expression in triple-negative breast cancer (TNBC) and its correlation with radiotherapy remains unknown. This study aimed to clarify the prognostic value of CXCR6 and its role in the breast tumor microenvironment (TME).

METHODS

The messenger RNA and protein expression of CXCR6 in human TNBC and their association with survival were analyzed. The role of CXCR6 in the immune context was investigated using a combination of single-cell RNA sequencing, bulk transcriptome sequencing data, and fluorescence-based multiplex immunohistochemistry (mIHC) techniques.

RESULTS

Elevated CXCR6 expression correlated with better clinical outcomes and superior response to adjuvant radiotherapy and immunotherapy in TNBC. CXCR6 fostered an immunostimulatory microenvironment characterized by upregulated cytotoxic markers. We also found that CXCR6 plays a crucial role in regulating the differentiation of CD8+ T cells and the intercellular communication of immune cell subtypes, thus shaping the TME.

CONCLUSIONS

This study highlights the emerging role of CXCR6 in shaping the TME and targeting CXCR6 may be a promising strategy for improving the effectiveness of radiotherapy and immunotherapy in TNBC.

摘要

背景

趋化因子受体 CXCR6 对于 CD8+ 细胞毒性 T 细胞（CTLs）在肿瘤中介导的持续肿瘤控制至关重要。先前的研究表明，电离辐射通过上调 CXCR6 诱导炎症免疫结构。然而，CXCR6 在三阴性乳腺癌（TNBC）中的表达及其与放疗的相关性的临床意义尚不清楚。本研究旨在阐明 CXCR6 的预后价值及其在乳腺肿瘤微环境（TME）中的作用。

方法

分析了人类 TNBC 中 CXCR6 的信使 RNA 和蛋白表达及其与生存的相关性。使用单细胞 RNA 测序、批量转录组测序数据和基于荧光的多重免疫组化（mIHC）技术相结合的方法研究了 CXCR6 在免疫环境中的作用。

结果

CXCR6 表达升高与 TNBC 更好的临床结局和对辅助放疗和免疫治疗的更好反应相关。CXCR6 促进了以细胞毒性标志物上调为特征的免疫刺激微环境。我们还发现，CXCR6 在调节 CD8+T 细胞的分化和免疫细胞亚型的细胞间通讯方面发挥着关键作用，从而塑造了 TME。

结论

本研究强调了 CXCR6 在塑造 TME 中的新作用，靶向 CXCR6 可能是提高 TNBC 中放疗和免疫治疗效果的有前途的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac63/11325934/aca3e67c8f1f/js9-110-4695-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac63/11325934/aca3e67c8f1f/js9-110-4695-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac63/11325934/aca3e67c8f1f/js9-110-4695-g007.jpg

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