Immune effects of CDK4/6 inhibitors in patients with HR+/HER2− metastatic breast cancer: Relief from immunosuppression is associated with clinical response

Autor: Fabio Scirocchi, Simone Scagnoli, Andrea Botticelli, Alessandra Di Filippo, Chiara Napoletano, Ilaria Grazia Zizzari, Lidia Strigari, Silverio Tomao, Enrico Cortesi, Aurelia Rughetti, Paolo Marchetti, Marianna Nuti
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: EBioMedicine, Vol 79, Iss , Pp 104010- (2022)
Druh dokumentu: article
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2022.104010
Popis: Summary: Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are innovative small target molecules that, in combination with endocrine therapy, have recently been employed in the treatment of patients with HR+/HER2− metastatic breast cancer (mBC). In this prospective study, we investigate the impact of CDK4/6i on the immune profile of patients with HR+/HER2− mBC. Methods: Immune cell subsets were analysed using flow cytometry of peripheral blood mononuclear cells (PBMCs) isolated from patients with HR+/HER2− mBC, both before and during treatment. Regulatory T cells (Tregs) were identified using the markers CD4, CD25, CTLA4, CD45RA, and intracellular FOXP3. Monocytic and polymorphonuclear myeloid-derived suppressor cells (M-MDSCs and PMN-MDSCs) and other immune populations were analysed using CD45, CD14, CD66b, CD11c, HLA-DR, CD3, CD8, CD28, CD137, PD1, CD45RA, CCR7, and Ki67. Findings: The percentage of circulating Tregs and M/PMN-MDSCs was significantly downregulated from baseline during CDK4/6i-treatment (p
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