Palbociclib and endocrine therapy diminish adaptive anti-tumor immunity in early breast cancer: The NeoRHEA phase 2 study
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.
Authors
- Andreas Papagiannis
- Patrick Neven (ORCID: https://orcid.org/0000-0002-1434-9460)
- Ahmad Awada (ORCID: https://orcid.org/0000-0001-7412-9163)
- Tatiana Besse Hammer
- Roberto Salgado (ORCID: https://orcid.org/0000-0002-1110-3801)
- Alexandra Stanciu (ORCID: https://orcid.org/0000-0002-5866-4200)
- Isabelle Veys (ORCID: https://orcid.org/0000-0002-7624-8075)
- François P. Duhoux (ORCID: https://orcid.org/0000-0002-5429-7888)
- Laurence Buisseret (ORCID: https://orcid.org/0000-0002-3751-0819)
- Peter Vuylsteke (ORCID: https://orcid.org/0000-0001-6401-3722)
- Timothy P. Cash
- Françoise Rothé (ORCID: https://orcid.org/0009-0003-2625-5642)
- Karen Willard‐Gallo (ORCID: https://orcid.org/0000-0002-1150-1295)
- Samira Majjaj (ORCID: https://orcid.org/0009-0000-7047-0663)
- Francesc Madriles (ORCID: https://orcid.org/0000-0002-5044-0747)
- Christos Sotiriou (ORCID: https://orcid.org/0000-0002-5745-9977)
- Marianne Paesmans
- Michail Ignatiadis (ORCID: https://orcid.org/0000-0002-4493-3748)
- Lieveke Ameye (ORCID: https://orcid.org/0000-0001-5153-1766)
- Elisa Agostinetto (ORCID: https://orcid.org/0000-0003-0295-7511)
- Thila Vanhulst (ORCID: https://orcid.org/0009-0006-4806-0370)
- Denis Larsimont
Institutions
- Institut d'Estadística de Catalunya (ES)
- Cliniques Universitaires Saint-Luc (BE)
- Université Libre de Bruxelles (BE)
- University of Namur (BE)
- Universitair Ziekenhuis Leuven (BE)
- Peter MacCallum Cancer Centre (AU)
- Institut Jules Bordet (BE)
- CHU Dinant Godinne UCL Namur (BE)
- Centre Hospitalier Universitaire Brugmann (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-26
- DOI
- https://doi.org/10.1038/s41467-025-66590-2
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pfizer