Suppr超能文献

对大量乳腺癌队列中的免疫浸润进行数据驱动分析及其与疾病进展、雌激素受体活性和基因组复杂性的关联。

Data-driven analysis of immune infiltrate in a large cohort of breast cancer and its association with disease progression, ER activity, and genomic complexity.

作者信息

Dannenfelser Ruth, Nome Marianne, Tahiri Andliena, Ursini-Siegel Josie, Vollan Hans Kristian Moen, Haakensen Vilde D, Helland Åslaug, Naume Bjørn, Caldas Carlos, Børresen-Dale Anne-Lise, Kristensen Vessela N, Troyanskaya Olga G

机构信息

Department of Computer Science, Princeton University, Princeton, New Jersey, United States of America.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States of America.

出版信息

Oncotarget. 2017 Jul 7;8(34):57121-57133. doi: 10.18632/oncotarget.19078. eCollection 2017 Aug 22.

Abstract

The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry. Herein we utilize a machine learning based approach to identify lymphocyte markers with which we can quantify the presence of B cells, cytotoxic T-lymphocytes, T-helper 1, and T-helper 2 cells in any gene expression data set and apply it to studies of breast tissue. By leveraging over 2,100 samples from existing large scale studies, we are able to find an inherent cell heterogeneity in clinically characterized immune infiltrates, a strong link between estrogen receptor activity and infiltration in normal and tumor tissues, changes with genomic complexity, and identify characteristic differences in lymphocyte expression among molecular groupings. With our extendable methodology for capturing cell type specific signal we systematically studied immune infiltration in breast cancer, finding an inverse correlation between beneficial lymphocyte infiltration and estrogen receptor activity in normal breast tissue and reduced infiltration in estrogen receptor negative tumors with high genomic complexity.

摘要

肿瘤微环境在肿瘤进展、治疗反应和临床结果中的作用现已得到广泛认可。特别是肿瘤内的免疫格局已被证明具有促肿瘤和抗肿瘤作用。识别免疫活性或免疫沉默的肿瘤可能是进行治疗的重要指征,而检测早期浸润模式可能会发现导致早期风险的因素。到目前为止,对肿瘤浸润细胞组成的直接详细研究一直有限;一些研究使用免疫组织化学进行大致定量,其他一些小型研究则通过从切除的肿瘤中分离细胞并使用流式细胞术对其进行分选来获得详细测量。在此,我们利用基于机器学习的方法来识别淋巴细胞标志物,通过这些标志物我们可以在任何基因表达数据集中量化B细胞、细胞毒性T淋巴细胞、辅助性T细胞1和辅助性T细胞2的存在,并将其应用于乳腺组织研究。通过利用来自现有大规模研究的2100多个样本,我们能够发现临床特征性免疫浸润中固有的细胞异质性、雌激素受体活性与正常和肿瘤组织浸润之间的紧密联系、随基因组复杂性的变化,并识别分子分组之间淋巴细胞表达的特征差异。通过我们用于捕获细胞类型特异性信号的可扩展方法,我们系统地研究了乳腺癌中的免疫浸润,发现正常乳腺组织中有益的淋巴细胞浸润与雌激素受体活性呈负相关,而在基因组复杂性高的雌激素受体阴性肿瘤中浸润减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c11c/5593630/04fe6d9e0fac/oncotarget-08-57121-g001.jpg

相似文献

5
Comprehensive evaluation of methods to assess overall and cell-specific immune infiltrates in breast cancer.
Breast Cancer Res. 2019 Dec 26;21(1):151. doi: 10.1186/s13058-019-1239-4.
6
The regulatory roles of T helper cells in distinct extracellular matrix characterization in breast cancer.
Front Immunol. 2022 Sep 8;13:871742. doi: 10.3389/fimmu.2022.871742. eCollection 2022.
8
Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study.
PLoS Med. 2016 Dec 13;13(12):e1002194. doi: 10.1371/journal.pmed.1002194. eCollection 2016 Dec.
10
Spatial Profiles of Intratumoral PD-1 Helper T Cells Predict Prognosis in Head and Neck Squamous Cell Carcinoma.
Front Immunol. 2021 Oct 28;12:769534. doi: 10.3389/fimmu.2021.769534. eCollection 2021.

引用本文的文献

1
Interaction between the breast tumor microenvironment and gut microbiome.
Gut Microbes. 2025 Dec;17(1):2514136. doi: 10.1080/19490976.2025.2514136. Epub 2025 Jun 8.
2
Regulation of Stromal Cells by Sex Steroid Hormones in the Breast Cancer Microenvironment.
Cancers (Basel). 2024 Dec 2;16(23):4043. doi: 10.3390/cancers16234043.
8
Identification of immunosuppressive signature subtypes and prognostic risk signatures in triple-negative breast cancer.
Front Oncol. 2023 Jun 12;13:1108472. doi: 10.3389/fonc.2023.1108472. eCollection 2023.
9
Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment.
ACS Omega. 2023 Mar 21;8(13):12217-12231. doi: 10.1021/acsomega.2c08227. eCollection 2023 Apr 4.
10
Estrogens, Cancer and Immunity.
Cancers (Basel). 2022 Apr 30;14(9):2265. doi: 10.3390/cancers14092265.

本文引用的文献

1
PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements.
Nucleic Acids Res. 2017 Jan 4;45(D1):D183-D189. doi: 10.1093/nar/gkw1138. Epub 2016 Nov 29.
3
Robust enumeration of cell subsets from tissue expression profiles.
Nat Methods. 2015 May;12(5):453-7. doi: 10.1038/nmeth.3337. Epub 2015 Mar 30.
4
Targeted exploration and analysis of large cross-platform human transcriptomic compendia.
Nat Methods. 2015 Mar;12(3):211-4, 3 p following 214. doi: 10.1038/nmeth.3249. Epub 2015 Jan 12.
5
Lymphocyte Invasion in IC10/Basal-Like Breast Tumors Is Associated with Wild-Type TP53.
Mol Cancer Res. 2015 Mar;13(3):493-501. doi: 10.1158/1541-7786.MCR-14-0387. Epub 2014 Oct 28.
6
A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.
Mol Oncol. 2015 Jan;9(1):115-27. doi: 10.1016/j.molonc.2014.07.019. Epub 2014 Aug 8.
7
Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients.
Ann Oncol. 2014 Aug;25(8):1536-43. doi: 10.1093/annonc/mdu191. Epub 2014 Jun 9.
8
TP53 mutation spectrum in breast cancer is subtype specific and has distinct prognostic relevance.
Clin Cancer Res. 2014 Jul 1;20(13):3569-80. doi: 10.1158/1078-0432.CCR-13-2943. Epub 2014 May 6.
10
Deregulation of cancer-related miRNAs is a common event in both benign and malignant human breast tumors.
Carcinogenesis. 2014 Jan;35(1):76-85. doi: 10.1093/carcin/bgt333. Epub 2013 Oct 8.

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