免疫系统
医学
内科学
外周血单个核细胞
免疫学
免疫疗法
癌症
T细胞
细胞因子
乳腺癌
癌症研究
肿瘤科
生物
生物化学
体外
作者
Caroline Anna Peuker,S Yaghobramzi,Corinna Grunert,Luisa Keilholz,Enio Gjerga,Steffen Hennig,Sigrid Schaper,Il‐Kang Na,Ulrich Keller,Sara Y. Brucker,Thomas Decker,Peter A. Fasching,Tanja Fehm,Wolfgang Janni,Sherko Kümmel,Andreas Schneeweiß,Martin Schüler,Diana Lüftner,Antonia Busse
标识
DOI:10.1016/j.ejca.2021.11.025
摘要
Inhibitors of the cyclin-dependent kinases 4 and 6 (CDK4/6i) have significantly improved clinical outcomes in patients with advanced hormone receptor-positive (HR+) breast cancer and have demonstrated favourable antitumour immune responses in preclinical studies.Here, we investigated peripheral immune responses to ribociclib in patients with metastatic HR+ breast cancer as a preplanned exploratory subanalysis of the RIBECCA trial (NCT03096847). Peripheral blood mononuclear cells were subjected to immune cell profiling, gene expression analysis of immune-related signatures, and deep T cell receptor profiling before treatment started and after 12 weeks of treatment with ribociclib.Gene expression analysis revealed an upregulation of signatures associated with an activated adaptive immune system and a decrease in immunosuppressive cytokine signalling during treatment with ribociclib. Profiling of peripheral immune cell subpopulations showed a decrease in Treg cell frequencies, which was associated with treatment response. Furthermore, induction of CD4+ naive T cells could be seen, whereas effector and memory T cell populations remained largely unchanged. Correspondingly, T cell repertoire diversity remained mostly unchanged during treatment, although an increase in clonality could be observed in single patients.We show that treatment with ribociclib has significant effects on the peripheral innate and adaptive immune response in patients with HR+ breast cancer. Our data suggest that these effects lead to an activation of an already existing immune response rather than a de novo induction and make a strong case for future combination strategies of CDK4/6i with immunotherapies to enhance the adaptive immune response in HR+ breast cancer.
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