Suppr超能文献

肿瘤引流淋巴结与冷型三阴性乳腺癌相关,其特征为与 Th2 相关的微环境。

Tumor draining lymph nodes connected to cold triple-negative breast cancers are characterized by Th2-associated microenvironment.

机构信息

Department of Immuno-Oncology, Beckman Research Institute, City of Hope, Duarte, CA, USA.

Irell & Manella Graduate School of Biological Sciences, City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.

出版信息

Nat Commun. 2024 Oct 4;15(1):8592. doi: 10.1038/s41467-024-52577-y.

Abstract

Tumor draining lymph nodes (TDLN) represent a key component of the tumor-immunity cycle. There are few studies describing how TDLNs impact lymphocyte infiltration into tumors. Here we directly compare tumor-free TDLNs draining "cold" and "hot" human triple negative breast cancers (TDLN and TDLN). Using machine-learning-based self-correlation analysis of immune gene expression, we find unbalanced intranodal regulations within TDLN. Two gene pairs (TBX21/GATA3-CXCR1) with opposite correlations suggest preferential priming of T helper 2 (Th2) cells by mature dendritic cells (DC) within TDLN. This is validated by multiplex immunofluorescent staining, identifying more mature-DC-Th2 spatial clusters within TDLN versus TDLN. Associated with this Th2 priming preference, more IL4 producing mast cells (MC) are found within sinus regions of TDLN. Downstream, Th2-associated fibrotic TME is found in paired cold tumors with increased Th2/T-helper-1-cell (Th1) ratio, upregulated fibrosis growth factors, and stromal enrichment of cancer associated fibroblasts. These findings are further confirmed in a validation cohort and public genomic data. Our results reveal a potential role of IL4 MCs within TDLNs, associated with Th2 polarization and reduced immune infiltration into tumors.

摘要

肿瘤引流淋巴结 (TDLN) 是肿瘤免疫循环的关键组成部分。目前很少有研究描述 TDLN 如何影响淋巴细胞浸润肿瘤。在这里,我们直接比较了无肿瘤 TDLN 引流的“冷”和“热”人类三阴性乳腺癌 (TDLN 和 TDLN)。我们使用基于机器学习的免疫基因表达自相关分析,发现 TDLN 内存在不平衡的腔内调节。两个具有相反相关性的基因对 (TBX21/GATA3-CXCR1) 提示成熟树突状细胞 (DC) 优先在 TDLN 内启动辅助性 T 细胞 2 (Th2) 细胞。这通过多重免疫荧光染色得到了验证,鉴定出 TDLN 中比 TDLN 更多的成熟-DC-Th2 空间簇。与这种 Th2 启动偏好相关的是,在 TDLN 的窦区发现了更多产生 IL4 的肥大细胞 (MC)。下游,在配对的冷肿瘤中发现了与 Th2 相关的纤维化 TME,其 Th2/T-helper-1-cell (Th1) 比值增加,纤维化生长因子上调,以及癌症相关成纤维细胞在基质中的富集。这些发现进一步在验证队列和公共基因组数据中得到了证实。我们的研究结果揭示了 TDLN 内 IL4 MC 的潜在作用,与 Th2 极化和肿瘤内免疫浸润减少有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e255/11452381/f4346abb0a89/41467_2024_52577_Fig1_HTML.jpg

相似文献

2
Defined Intestinal Regions Are Drained by Specific Lymph Nodes That Mount Distinct Th1 and Th2 Responses Against Eggs.
Front Immunol. 2020 Oct 23;11:592325. doi: 10.3389/fimmu.2020.592325. eCollection 2020.
4
Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.
Sci Rep. 2024 May 21;14(1):11576. doi: 10.1038/s41598-024-60243-y.
8
Basophil Recruitment into Tumor-Draining Lymph Nodes Correlates with Th2 Inflammation and Reduced Survival in Pancreatic Cancer Patients.
Cancer Res. 2016 Apr 1;76(7):1792-803. doi: 10.1158/0008-5472.CAN-15-1801-T. Epub 2016 Feb 12.
10
Immune microenvironment of tumor-draining lymph nodes: insights for immunotherapy.
Front Immunol. 2025 Apr 11;16:1562797. doi: 10.3389/fimmu.2025.1562797. eCollection 2025.

引用本文的文献

1
Boosting Dendritic Cell Function in Cancer.
Cancer Med. 2025 Sep;14(17):e71062. doi: 10.1002/cam4.71062.
2
Mast cells boost anti-tumor potency of MAIT cells via inflammasome-dependent secretion of IL-18.
Nat Commun. 2025 Jul 2;16(1):6074. doi: 10.1038/s41467-025-61324-w.
3
SMYD3 Promotes Immune Evasion in Clear Cell Renal Cell Carcinoma via SREBP1-Mediated Transactivation of CD47.
Adv Sci (Weinh). 2025 Sep;12(34):e04200. doi: 10.1002/advs.202404200. Epub 2025 Jun 23.
5
The Impact of Mast Cells on the Anatomy, Cellular Communication, and Molecular Immune Network of Lymph Nodes.
Clin Rev Allergy Immunol. 2025 Apr 2;68(1):35. doi: 10.1007/s12016-025-09050-5.

本文引用的文献

1
Slide-tags enables single-nucleus barcoding for multimodal spatial genomics.
Nature. 2024 Jan;625(7993):101-109. doi: 10.1038/s41586-023-06837-4. Epub 2023 Dec 13.
2
A telencephalon cell type atlas for goldfish reveals diversity in the evolution of spatial structure and cell types.
Sci Adv. 2023 Nov 3;9(44):eadh7693. doi: 10.1126/sciadv.adh7693. Epub 2023 Nov 1.
4
Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer.
J Transl Med. 2022 Dec 23;20(1):615. doi: 10.1186/s12967-022-03807-8.
5
Cancer Associated Fibroblasts - An Impediment to Effective Anti-Cancer T Cell Immunity.
Front Immunol. 2022 Apr 11;13:887380. doi: 10.3389/fimmu.2022.887380. eCollection 2022.
7
Comprehensive evaluation of deconvolution methods for human brain gene expression.
Nat Commun. 2022 Mar 15;13(1):1358. doi: 10.1038/s41467-022-28655-4.
8
Spatial CRISPR genomics identifies regulators of the tumor microenvironment.
Cell. 2022 Mar 31;185(7):1223-1239.e20. doi: 10.1016/j.cell.2022.02.015. Epub 2022 Mar 14.
10
Lymph Node Immune Profiles as Predictive Biomarkers for Immune Checkpoint Inhibitor Response.
Front Mol Biosci. 2021 May 24;8:674558. doi: 10.3389/fmolb.2021.674558. eCollection 2021.

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