Wei Yuhan, Ge Hewei, Qi Yalong, Zeng Cheng, Sun Xiaoying, Mo Hongnan, Ma Fei
Department 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, China.
Department of Medical Oncology, Cancer Hospital of HuanXing ChaoYang District, Beijing, China.
Clin Transl Med. 2025 Mar;15(3):e70255. doi: 10.1002/ctm2.70255.
Immunotherapy shows promise for treating advanced breast cancer, but only a few patients could respond. Predictive biomarkers from peripheral blood are urgently needed.
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.
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).
Peripheral CD39+ Tregs and monocyte-derived dendritic cells are correlated with immunotherapy response, serving as potential biomarkers to guide therapeutic choices in immunotherapy.
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.
免疫疗法在治疗晚期乳腺癌方面显示出前景，但只有少数患者有反应。迫切需要外周血中的预测性生物标志物。
我们设计了一个包含42个标志物的综合质谱流式细胞术检测板，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，随后进行表型和功能比较以确定候选预测性生物标志物。对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。
在基线时，无反应者的T细胞环境中CD39+调节性T细胞（Tregs）频率显著更高（校正p = 0.031），在无反应组中其与PD-1+ T细胞呈正相关。纵向评估表明，抗PD-1治疗后PD-1+ T细胞显著减少，CD39+ Tregs增加，提示它们在免疫治疗耐药中可能起作用。在髓系细胞中，反应者的CCR2+单核细胞衍生树突状细胞频率显著高于无反应者（校正p = 0.037）。这些细胞在反应者中与其他树突状细胞呈正相关，但在无反应者中与初始T细胞呈负相关。基于这两种与疗效相关的生物标志物，我们开发了一种免疫治疗预后预测模型，并证实其在区分患者PFS方面的优越性（p < 0.001）。
外周血CD39+ Tregs和单核细胞衍生树突状细胞与免疫治疗反应相关，可作为指导免疫治疗中治疗选择的潜在生物标志物。
外周血中的CD39+ Tregs与晚期乳腺癌抗PD-1免疫治疗反应不佳相关。CCR2+单核细胞衍生树突状细胞频率较高与更好的免疫治疗结果相关。基于CD39+ Tregs和单核细胞衍生树突状细胞的预测模型可有效区分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方法来指导免疫治疗选择。
