Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study.
(2025) Nature Communications — Vol. 2025, n° 2025, p. 1-31 (2025)
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- Authors
Agostinetto, Elisa 
Ignatiadis, Michail
- Abstract
- The NeoRHEA was a single-arm phase 2 study that included patients with estrogen receptor positive / human epidermal factor receptor 2 negative early breast cancer that received 4 cycles of neoadjuvant palbociclib and endocrine therapy. The primary outcome was baseline biomarkers of treatment resistance and secondary outcome was post-treatment transcriptional and epigenetic changes of tumor, immune and stromal cells. E2F targets and G2M checkpoint proliferation-related genes gene sets were enriched in baseline samples from resistant patients., Downregulation of E2F targets and G2M checkpoint post treatment was observed in tumor, endothelial and T cells. Gene Set Enrichment Analyses (GSEA) based on genes residing in the differentially accessible peaks revealed similar effects,. Moreover, decreases in CD8 + CD103+ tissue-resident memory cell marker genes were observed post-treatment and validated by multiplex immunohistochemistry. Our data reveal that treatment with palbociclib and endocrine therapy diminishes adaptive anti-tumor immunity by decreasing T cell proliferation and the presence of tissue-resident memory T cells NCT03065621.
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Citations
Papagiannis, A., Majjaj, S., Duhoux, F., Agostinetto, E., Stanciu, A. M., Vanhulst, T., Buisseret, L., Larsimont, D., Veys, I., Paesmans, M., Hammer, T. B., Awada, A., Ameye, L., Rothe, F., Madriles, F., Cash, T. P., Salgado, R., Willard-Gallo, K., Sotiriou, C., et al. (2025). Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study. Nature Communications, 2025(2025), 1-31. https://doi.org/10.1038/s41467-025-66590-2 (Original work published 2025)