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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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.