Tumor-stroma proportion is associated with increased M2 macrophage abundance and predicts the resistance to immune checkpoint blockade in breast cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2025-03-10 DOI:10.1016/j.tranon.2025.102343

Yincheng Liu , Ningyi Xue , Yuelin Liu , Jie Mei , Yun Cai , Zhenghui Wang , Hongxin Lin , Mengyun Wan , Ji Zhou , Tiansong Xia , Yichao Zhu , Shui Wang

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引用次数: 0

Abstract

Background

The tumor stroma has been reported to be associated with worse prognosis in several solid tumors, but its prognostic value in breast cancer (BRCA) is still undefined.

Methods

In this research, multiple public and in-house patient cohorts were collected to demonstrate the clinical and immune correlations of tumor-stroma proportion (TSP) in BRCA. In addition, in vitro assays uncovered the oncogenic role of TSP-related collagen in BRCA.

Results

High TSP status based on hematoxylin and eosin (HE) staining was associated with positive hormone receptor status, advanced clinical stages, and poor immune checkpoint blockade (ICB) response. In addition, we developed a RNA-sequencing (RNA-seq)-based stromal score based on four critical genes expression (AEBP1, COL6A3, CTSK, and PLAC9). Both TSP status and stromal score were positively associated with increased M2 macrophage abundance in BRCA. Moreover, tumor collagen has been found to be enriched in samples with the high TSP status, and collagen promoted BRCA cells aggressiveness and macrophage M2 polarization.

Conclusions

The tumor stroma was found to be notably related to poor ICB response in patients with BRCA as a result of tumor stroma-macrophage interactions. Thus, the TSP status could predict the clinical outcomes of BRCA patients receiving ICB therapy.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.