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

Papagiannis, A; Majjaj, S; Duhoux, FP; Agostinetto, E; Stanciu, AM; Vanhulst, T; Buisseret, L; Larsimont, D; Veys, I; Paesmans, M; Hammer, TB; Awada, A; Ameye, L; Rothe, F; Madriles, F; Cash, TP; Salgado, R; Willard-Gallo, K; Sotiriou, C; Vuylsteke, P; Neven, P; Ignatiadis, M

Author(s): Papagiannis, A; Majjaj, S; Duhoux, FP; Agostinetto, E; Stanciu, AM; Vanhulst, T; Buisseret, L; Larsimont, D; Veys, I; Paesmans, M; Hammer, TB; Awada, A; Ameye, L; Rothe, F; Madriles, F; Cash, TP; Salgado, R; Willard-Gallo, K; Sotiriou, C; Vuylsteke, P; Neven, P; Ignatiadis, M;
Details: Publication Year 2025-11-26,Volume 16,Issue #1,Page 11659
Journal Title: Nature Communications
Publication Type: Research article
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.
Publisher: Springer Nature
Keywords: Humans; *Breast Neoplasms/drug therapy/immunology/genetics/pathology; Female; *Pyridines/therapeutic use/administration & dosage/pharmacology; *Piperazines/therapeutic use/administration & dosage/pharmacology; Middle Aged; *Adaptive Immunity/drug effects; Receptor, ErbB-2/metabolism; Adult; Neoadjuvant Therapy; Aged; Gene Expression Regulation, Neoplastic/drug effects; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41467-025-66590-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-025-66590-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-12-05 02:49:46

Last Modified: 2026-01-13 05:40:51