Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2...

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Estrogen receptor-positive/human epidermal factor receptor 2-negative (ER+/HER2-) early breast cancer is a common subtype.
• Neoadjuvant therapy aims to shrink tumors before surgery, improving outcomes.
• Understanding treatment resistance mechanisms is crucial for optimizing therapy.

Purpose of the Study:

• To investigate baseline biomarkers associated with treatment resistance in ER+/HER2- early breast cancer.
• To analyze post-treatment transcriptional and epigenetic changes in tumor, immune, and stromal cells.
• To evaluate the impact of neoadjuvant palbociclib and endocrine therapy on anti-tumor immunity.

Main Methods:

• Single-arm phase 2 clinical trial (NeoRHEA study).
• Analysis of baseline and post-treatment tumor samples.
• Gene Set Enrichment Analysis (GSEA) to identify enriched gene sets.
• Multiplex immunohistochemistry to validate immune cell marker changes.

Main Results:

• Baseline samples from resistant patients showed enrichment in E2F targets and G2M checkpoint proliferation-related genes.
• Post-treatment, downregulation of E2F targets and G2M checkpoint genes was observed in tumor, endothelial, and T cells.
• A decrease in CD8+ CD103+ tissue-resident memory T cell markers was noted post-treatment.

Conclusions:

• Neoadjuvant palbociclib and endocrine therapy may diminish adaptive anti-tumor immunity.
• The treatment decreases T cell proliferation and the presence of tissue-resident memory T cells.
• Further research is needed to understand and potentially overcome treatment-induced immune suppression.