Loading
Life sciences · Journal article
Communications Medicine · September 19, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
Advanced HER2-negative breast cancer remains difficult to treat, and mechanisms associated with response to immunotherapy-based combinations are not fully understood. This study aimed to characterize therapeutic response pathways in patients treated with entinostat and dual immune checkpoint inhibitors (nivolumab and ipilimumab). We analyzed 37 tumor biopsies from 19 patients enrolled in a Phase Ib trial (NCT02453620). Samples from six metastatic sites were collected at baseline, post-entinostat run-in (C1D1), and post-triplet therapy (week 8). Using bulk RNA-seq, T-cell receptor repertoire (TCR), and neoantigen data, we evaluated gene expression changes and immune-related features associated with clinical response. Here we show that differential gene expression revealed immune-related pathway changes, including interferon responses, IL6/JAK/STAT3, and IL2/STAT5 signaling. Responders show baseline enrichment of inflammatory and interferon pathways, suggesting a more immune-active tumor microenvironment (TME). Post-entinostat, responders show a trend toward increased expression of CD8 + T-cell and plasma cell markers, suggesting partial TME modulation. After triplet therapy, genes linked to M1-like macrophages, pDCs, memory T and B cells, NK cells, and Th1 cells are significantly altered. PAM50 analysis shows that basal and luminal B subtypes correlated with response. TCR diversity inferred from RNA-seq is higher in responders, while neoantigen analysis revealed fewer strong binders at week 8. These findings suggest that entinostat in combination with anti-CTLA-4 and anti-PD-1 therapies facilitates changes within the TME that may promote response in advanced HER2-negative breast cancer. Although the small and heterogeneous cohort limits definitive conclusions, the results identify biological features associated with response and support further investigation of this therapeutic strategy. Advanced HER2-negative breast cancer can be difficult to treat, and many patients do not benefit from immunotherapy. This study investigated whether a combination of three drugs—entinostat, nivolumab, and ipilimumab—could alter the tumor environment in ways that support an anti-cancer immune response. We analyzed tumor samples from 19 patients collected before and during treatment, and examined changes in gene activity, immune cells, and tumor-related markers over time. Patients who responded to treatment showed signs of a more active immune environment before treatment began. Treatment was also associated with changes in several immune pathways and cell types linked to anti-tumor activity. These findings suggest that this drug combination may help stimulate immune responses in some patients with advanced breast cancer and may inform future treatment strategies.