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多形性乳腺癌常表达免疫检查点标志物 FOXP3 和 PD-L1。

Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1.

机构信息

Faculty of Medicine, UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, QLD, Australia.

QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia.

出版信息

Br J Cancer. 2020 Nov;123(11):1665-1672. doi: 10.1038/s41416-020-01065-3. Epub 2020 Sep 17.


DOI:10.1038/s41416-020-01065-3
PMID:32939056
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7686342/
Abstract

BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets. METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data. RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.

摘要

背景: 化生性乳腺癌包含一组具有分化为鳞状和/或梭形、软骨样、骨样或横纹肌样间充质样成分的异质性肿瘤。新兴的免疫疗法靶向程序性死亡配体 1(PD-L1)和免疫抑制性 T 细胞(Tregs)可能使化生性乳腺癌患者受益,这些患者通常对化疗耐药,并且不表达激素治疗靶点。 方法: 我们评估了 PD-L1 和 FOXP3 的免疫组化表达以及肿瘤浸润淋巴细胞(TILs)的程度,这些化生性乳腺癌患者具有生存数据。 结果: 与三阴性导管乳腺癌相比,化生性乳腺癌中 PD-L1 阳性肿瘤细胞明显更丰富(P<0.0001),而 PD-L1 阳性 TILs 则没有显著差异。化生性乳腺癌中 TILs 表达 FOXP3 的比例也明显更高,FOXP3 阳性肿瘤内 TILs(iTILs)与不良预后相关(P=0.0226)。多变量分析确定 FOXP3 iTILs 表达状态是患者生存的重要独立预后因素。 结论: 我们的研究结果表明,FOXP3、PD-1/PD-L1 检查点和 TILs 在化生性乳腺癌中的临床意义和预后价值,并证实了一部分化生性乳腺癌可能受益于免疫治疗。

相似文献

[1]
Metaplastic breast cancers frequently express immune checkpoint markers FOXP3 and PD-L1.

Br J Cancer. 2020-11

[2]
Integration of tumour infiltrating lymphocytes, programmed cell-death ligand-1, CD8 and FOXP3 in prognostic models for triple-negative breast cancer: Analysis of 244 stage I-III patients treated with standard therapy.

Eur J Cancer. 2020-9

[3]
The predictive and prognostic value of Foxp3+/CD25+ regulatory T cells and PD-L1 expression in triple negative breast cancer.

Ann Diagn Pathol. 2019-4-10

[4]
LAG-3+ tumor infiltrating lymphocytes in breast cancer: clinical correlates and association with PD-1/PD-L1+ tumors.

Ann Oncol. 2017-12-1

[5]
The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC).

Breast Cancer. 2017-5-9

[6]
Evaluation of immune density, PD-L1, and CXCR4 expressions in metaplastic breast carcinoma to predict potential immunotherapy benefit.

Med Oncol. 2023-12-15

[7]
The role of immune microenvironment in small-cell lung cancer: Distribution of PD-L1 expression and prognostic role of FOXP3-positive tumour infiltrating lymphocytes.

Eur J Cancer. 2018-8-1

[8]
Immune parameters associated with survival in metaplastic breast cancer.

Breast Cancer Res. 2020-8-18

[9]
PD-L1 expression in tumor infiltrated lymphocytes predicts survival in triple-negative breast cancer.

Pathol Res Pract. 2019-12-24

[10]
Tumor-infiltrating lymphocyte abundance and programmed death-ligand 1 expression in metaplastic breast carcinoma: implications for distinct immune microenvironments in different metaplastic components.

Virchows Arch. 2021-4

引用本文的文献

[1]
Neoadjuvant Versus Adjuvant Therapy for Metaplastic Breast Cancer: Insights from the National Cancer Database-Is There a Winning Strategy?

Ann Surg Oncol. 2025-9-10

[2]
Neoadjuvant Chemotherapy is Associated with Worse 5-Year Overall Survival in Patients with Metaplastic Breast Cancer Compared with Primary Surgery: A National Cancer Database Analysis.

Ann Surg Oncol. 2025-8-20

[3]
Integrated profiling of metaplastic breast cancer identifies putative master regulators of intratumoral heterogeneity.

NPJ Breast Cancer. 2025-8-11

[4]
Identification of M1 macrophage infiltration-related genes for immunotherapy in Her2-positive breast cancer based on bioinformatics analysis and machine learning.

Sci Rep. 2025-4-11

[5]
Novel models based on machine learning to predict the prognosis of metaplastic breast cancer.

Breast. 2025-2

[6]
Coordinated inflammation and immune response transcriptional regulation in breast cancer molecular subtypes.

Front Immunol. 2024

[7]
A comprehensive overview of metaplastic breast cancer: Features and treatments.

Cancer Sci. 2024-8

[8]
Translational Aspects in Metaplastic Breast Carcinoma.

Cancers (Basel). 2024-4-7

[9]
Starfysh integrates spatial transcriptomic and histologic data to reveal heterogeneous tumor-immune hubs.

Nat Biotechnol. 2025-2

[10]
The cellular composition of the tumor microenvironment is an important marker for predicting therapeutic efficacy in breast cancer.

Front Immunol. 2024

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