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

par Papagiannis, Andreas ;Majjaj, Samira ;Duhoux, Francois P;Agostinetto, Elisa ;Stanciu, Maria-Alexandra ;Vanhulst, Thila ;Buisseret, Laurence ;Larsimont, Denis ;Veys, Isabelle;Paesmans, Marianne ;Hammer, Tatiana Besse;Awada, Ahmad;Ameye, Lieveke;Rothe, Francoise;Madriles, Francesc;Cash, Timothy TP;Salgado, Roberto;Willard-Gallo, Karen;Sotiriou, Christos ;Vuylsteke, Peter;Neven, Patrick;Ignatiadis, Michail
Référence Nature communications
Publication Publié, 2025-11

Article révisé par les pairs

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Résumé :

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.