Suppr超能文献

浸润肿瘤的耗竭型 CD8+T 细胞预示着绝经前雌激素受体阳性乳腺癌患者生存时间缩短。

Tumor-infiltrating exhausted CD8+ T cells dictate reduced survival in premenopausal estrogen receptor-positive breast cancer.

机构信息

Department of Immuno-Oncology, Beckman Research Institute.

Light Microscopy Digital Imaging Core, Beckman Research Institute.

出版信息

JCI Insight. 2022 Feb 8;7(3):e153963. doi: 10.1172/jci.insight.153963.

Abstract

CD8+ tumor-infiltrating lymphocytes (TILs) are associated with improved survival in triple-negative breast cancer (TNBC) yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identified subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibited a distinct tumor microenvironment marked by amplified interferon-γ signaling-related pathways and higher programmed death ligand 1 expression. Paradoxically, higher levels of tumor-infiltrating CD8+ TEX associated with decreased overall survival of patients with ER+ BC but not patients with TNBC. Moreover, high tumor expression of a CD8+ TEX signature identified dramatically reduced survival in premenopausal, but not postmenopausal, patients with ER+ BC. Finally, we demonstrated the value of a tumor TEX signature score in identifying high-risk premenopausal ER+ BC patients among those with intermediate Oncotype DX Breast Recurrence Scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and ER status in BC patient survival. This work identifies tumor-infiltrating CD8+ TEX as a key feature of reduced survival outcomes in premenopausal patients with early-stage ER+ BC.

摘要

CD8+ 肿瘤浸润淋巴细胞(TILs)与三阴性乳腺癌(TNBC)的生存改善相关,但与雌激素受体阳性(ER+)BC 的生存无关。这些对比发现的基础仍然难以捉摸。我们确定了浸润 CD8+ T 细胞的 BC 肿瘤亚群,这些细胞具有耗尽 T 细胞(TEX)的特征。富含 CD8+TEX 的肿瘤表现出独特的肿瘤微环境,其特征是干扰素-γ 信号相关途径的扩增和程序性死亡配体 1 表达增加。矛盾的是,较高水平的肿瘤浸润 CD8+TEX 与 ER+BC 患者的总生存期降低相关,但与 TNBC 患者无关。此外,肿瘤中 CD8+TEX 特征的高表达与 ER+BC 绝经前患者的生存率明显降低有关,但与绝经后患者无关。最后,我们证明了肿瘤 TEX 特征评分在识别 Oncotype DX 乳腺复发评分中等的 ER+BC 绝经前高危患者中的价值。我们的数据强调了 CD8+TILs、干扰素-γ 信号和 ER 状态在 BC 患者生存中的复杂关系。这项工作确定了肿瘤浸润性 CD8+TEX 是 ER+BC 绝经前早期患者生存结局降低的关键特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c868/8855819/41e835ffd6cd/jciinsight-7-153963-g084.jpg

相似文献

7
Tumor microenvironment in triple-negative breast cancer: the correlation of tumor-associated macrophages and tumor-infiltrating lymphocytes.
Clin Transl Oncol. 2021 Dec;23(12):2513-2525. doi: 10.1007/s12094-021-02652-3. Epub 2021 Jun 5.
8
The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis.
Breast Cancer Res Treat. 2014 Dec;148(3):467-76. doi: 10.1007/s10549-014-3185-2. Epub 2014 Nov 1.

引用本文的文献

1
Tumour-infiltrating lymphocyte therapy landscape: prospects and challenges.
BMJ Oncol. 2025 Aug 4;4(1):e000566. doi: 10.1136/bmjonc-2024-000566. eCollection 2025.
2
HIV status alters immune cell infiltration and activation profile in women with breast cancer.
Nat Commun. 2025 May 20;16(1):4699. doi: 10.1038/s41467-025-59408-8.
4
Cytotoxic KLRG1+ IL-7R- effector CD8+ T cells distinguish kidney transplant recipients controlling cytomegalovirus reactivation.
Front Immunol. 2025 Feb 14;16:1542531. doi: 10.3389/fimmu.2025.1542531. eCollection 2025.
5
Advancements in the Application of scRNA-Seq in Breast Research: A Review.
Int J Mol Sci. 2024 Dec 22;25(24):13706. doi: 10.3390/ijms252413706.
6
CD8 T cell exhaustion in the tumor microenvironment of breast cancer.
Front Immunol. 2024 Dec 9;15:1507283. doi: 10.3389/fimmu.2024.1507283. eCollection 2024.
9
Integrative Pan-Cancer Analysis Reveals the Oncogenic Role of MND1 and Validation of MND1's Role in Breast Cancer.
J Inflamm Res. 2024 Jul 17;17:4721-4746. doi: 10.2147/JIR.S458832. eCollection 2024.

本文引用的文献

3
Resident memory CD8+ T cells within cancer islands mediate survival in breast cancer patients.
JCI Insight. 2019 Oct 3;4(19):130000. doi: 10.1172/jci.insight.130000.
4
Comprehensive Integration of Single-Cell Data.
Cell. 2019 Jun 13;177(7):1888-1902.e21. doi: 10.1016/j.cell.2019.05.031. Epub 2019 Jun 6.
5
Determining cell type abundance and expression from bulk tissues with digital cytometry.
Nat Biotechnol. 2019 Jul;37(7):773-782. doi: 10.1038/s41587-019-0114-2. Epub 2019 May 6.
6
A Single-Cell Atlas of the Tumor and Immune Ecosystem of Human Breast Cancer.
Cell. 2019 May 16;177(5):1330-1345.e18. doi: 10.1016/j.cell.2019.03.005. Epub 2019 Apr 11.
7
Dynamics of breast-cancer relapse reveal late-recurring ER-positive genomic subgroups.
Nature. 2019 Mar;567(7748):399-404. doi: 10.1038/s41586-019-1007-8. Epub 2019 Mar 13.
8
Subsets of exhausted CD8 T cells differentially mediate tumor control and respond to checkpoint blockade.
Nat Immunol. 2019 Mar;20(3):326-336. doi: 10.1038/s41590-019-0312-6. Epub 2019 Feb 18.
9
Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers.
J Clin Invest. 2019 Apr 1;129(4):1785-1800. doi: 10.1172/JCI96313. Epub 2019 Mar 18.
10
CD8 T Cell Exhaustion During Chronic Viral Infection and Cancer.
Annu Rev Immunol. 2019 Apr 26;37:457-495. doi: 10.1146/annurev-immunol-041015-055318. Epub 2019 Jan 24.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验