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Transcriptional and Epigenetic Changes Induced by CDK4/6 Inhibitors in Combination With Endocrine Therapy in Early Breast Cancer

par Papagiannis, Andreas
Président du jury Maenhaut, Carine
Promoteur Ignatiadis, Michail
Publication Non publié, 2025-04-28

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Résumé :

While the impact of palbociclib and endocrine therapy on breast cancer cells has been well-documented, there is a lack of data regarding their effects on immune and stromal cells within patient tumors. To explore this, single-nuclei RNA and ATAC sequencing were performed on tumor samples from breast cancer patients in the NeoRHEA trial, both before and after 4 months of treatment with palbociclib and endocrine therapy. The results showed a downregulation of E2F targets and G2M checkpoint genes related to proliferation across tumor cells, endothelial cells, and T-cells after treatment. Gene set enrichment analysis (GSEA) of genes within the differentially accessible peaks revealed similar patterns, suggesting that the changes in gene expression are linked to altered chromatin accessibility. Additionally, a reduction in CD8+/CD103+ tissue-resident memory T cells was noted post-treatment, and these findings were confirmed through multiplex immunohistochemistry. Overall, the treatment with palbociclib and endocrine therapy appears to impair adaptive anti-tumor immunity by reducing both T cell proliferation and the presence of tissue-resident memory T cells.