Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer
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...
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Wiley
2025-03-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.70255 |
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| author | Yuhan Wei Hewei Ge Yalong Qi Cheng Zeng Xiaoying Sun Hongnan Mo Fei Ma |
| author_facet | Yuhan Wei Hewei Ge Yalong Qi Cheng Zeng Xiaoying Sun Hongnan Mo Fei Ma |
| author_sort | Yuhan Wei |
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| description | 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. |
| format | Article |
| id | doaj-art-54743f1b2fc94c45bd1f2dbda3b682af |
| institution | Kabale University |
| issn | 2001-1326 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj-art-54743f1b2fc94c45bd1f2dbda3b682af2025-08-20T03:47:36ZengWileyClinical and Translational Medicine2001-13262025-03-01153n/an/a10.1002/ctm2.70255Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancerYuhan Wei0Hewei Ge1Yalong Qi2Cheng Zeng3Xiaoying Sun4Hongnan Mo5Fei Ma6Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology Cancer Hospital of HuanXing ChaoYang District Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract 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.https://doi.org/10.1002/ctm2.70255breast cancerCyTOFimmunotherapyPD‐1peripheral blood mononuclear cellpredictive biomarkers |
| spellingShingle | Yuhan Wei Hewei Ge Yalong Qi Cheng Zeng Xiaoying Sun Hongnan Mo Fei Ma Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer Clinical and Translational Medicine breast cancer CyTOF immunotherapy PD‐1 peripheral blood mononuclear cell predictive biomarkers |
| title | Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer |
| title_full | Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer |
| title_fullStr | Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer |
| title_full_unstemmed | Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer |
| title_short | Predictive circulating biomarkers of the response to anti‐PD‐1 immunotherapy in advanced HER2 negative breast cancer |
| title_sort | predictive circulating biomarkers of the response to anti pd 1 immunotherapy in advanced her2 negative breast cancer |
| topic | breast cancer CyTOF immunotherapy PD‐1 peripheral blood mononuclear cell predictive biomarkers |
| url | https://doi.org/10.1002/ctm2.70255 |
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