Predictive circulating biomarkers of the response to anti-PD-1 immunotherapy in advanced HER2 negative breast cancer

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2025-02-25 DOI:10.1002/ctm2.70255

Yuhan Wei, Hewei Ge, Yalong Qi, Cheng Zeng, Xiaoying Sun, Hongnan Mo, Fei Ma

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Abstract

Background

Immunotherapy shows promise for treating advanced breast cancer, but only a few patients could respond. Predictive biomarkers from peripheral blood are urgently needed.

Methods

We designed a comprehensive 42-marker mass cytometry panel to profile the peripheral blood samples from 57 patients diagnosed with advanced HER2-negative breast cancer receiving anti-PD-1 combination therapy. Patients were categorized as responders and non-responders according to 6-month progression-free survival (PFS), followed by phenotypic and functional comparations to identify candidate predictive biomarkers. Longitudinal analysis of paired samples further revealed dynamic changes in these specific subpopulations.

Results

Non-responders exhibited significantly higher frequencies of CD39+ Tregs (adjusted p = .031) in the T-cell milieu at baseline, which exhibited a positive correlation with PD-1+ T cells in the NR group. Longitudinal assessment indicated a significant decrease of PD-1+ T cells and an increase of CD39+ Tregs following anti-PD-1 treatment, suggesting their potential role in immunotherapy resistance. In the myeloid compartment, responders showed significantly higher CCR2+ monocyte-derived dendritic cell frequencies than non-responders (adjusted p = .037). These cells were positively correlated with other dendritic cells in responders but negatively with naïve T cells in non-responders. Based on these two efficacy-related biomarkers, we developed an immunotherapy prognostic prediction model and confirmed its superiority in distinguishing patient PFS (p < .001).

Conclusion

Peripheral CD39+ Tregs and monocyte-derived dendritic cells are correlated with immunotherapy response, serving as potential biomarkers to guide therapeutic choices in immunotherapy.

Key points

CD39+ Tregs in peripheral blood are associated with poor response to anti-PD-1 immunotherapy in advanced breast cancer.
Higher frequencies of CCR2+ monocyte-derived dendritic cells correlate with better immunotherapy outcomes.
A predictive model based on CD39+ Tregs and monocyte-derived dendritic cells effectively distinguishes patient progression-free survival.
Peripheral blood biomarkers offer a non-invasive approach to guide immunotherapy choices.

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晚期HER2阴性乳腺癌抗pd -1免疫治疗反应的预测性循环生物标志物

免疫疗法有望治疗晚期乳腺癌，但只有少数患者有疗效。迫切需要来自外周血的预测性生物标志物。方法我们设计了一个综合的42个标志物的细胞计数仪，对57例接受抗pd -1联合治疗的晚期her2阴性乳腺癌患者的外周血样本进行分析。根据6个月无进展生存期（PFS）将患者分为反应者和无反应者，然后进行表型和功能比较，以确定候选的预测性生物标志物。配对样本的纵向分析进一步揭示了这些特定亚群的动态变化。结果无应答者在基线时T细胞环境中CD39+ Tregs的频率显著高于对照组（p = 0.031），与NR组PD-1+ T细胞呈正相关。纵向评估显示，抗PD-1治疗后PD-1+ T细胞显著减少，CD39+ Tregs显著增加，提示它们在免疫治疗耐药中可能起作用。在髓系间室中，应答者的CCR2+单核细胞来源的树突状细胞频率明显高于无应答者（调整p = 0.037）。这些细胞在应答者中与其他树突状细胞正相关，而在无应答者中与naïve T细胞负相关。基于这两个疗效相关的生物标志物，我们建立了一个免疫治疗预后预测模型，并证实了其在区分PFS患者方面的优势(p <；措施)。结论外周血CD39+ Tregs和单核细胞来源的树突状细胞与免疫治疗反应相关，可作为指导免疫治疗选择的潜在生物标志物。外周血CD39+ Tregs与晚期乳腺癌抗pd -1免疫治疗反应差相关更高频率的CCR2+单核细胞衍生的树突状细胞与更好的免疫治疗结果相关。基于CD39+ Tregs和单核细胞来源的树突状细胞的预测模型有效地区分了患者的无进展生存期。外周血生物标志物提供了一种非侵入性的方法来指导免疫治疗的选择。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.