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Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer: findings from the RIBECCA trial

Background - 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. - Methods - Here, we in...

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Main Authors: Peuker, Caroline Anna (Author) , Yaghobramzi, Sarvenaz (Author) , Grunert, Corinna (Author) , Keilholz, Luisa (Author) , Gjerga, Enio (Author) , Hennig, Steffen (Author) , Schaper, Sigrid (Author) , Na, Il-Kang (Author) , Keller, Ulrich (Author) , Brucker, Sara (Author) , Decker, Thomas (Author) , Fasching, Peter (Author) , Fehm, Tanja (Author) , Janni, Wolfgang (Author) , Kümmel, Sherko (Author) , Schneeweiss, Andreas (Author) , Schuler, Martin (Author) , Lüftner, Diana (Author) , Busse, Antonia (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: European journal of cancer
Year: 2022, Volume: 162, Pages: 45-55
ISSN:1879-0852
DOI:10.1016/j.ejca.2021.11.025
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.ejca.2021.11.025
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0959804921012454
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Author Notes:Caroline A. Peuker, Sarvenaz Yaghobramzi, Corinna Grunert, Luisa Keilholz, Enio Gjerga, Steffen Hennig, Sigrid Schaper, Il-Kang Na, Ulrich Keller, Sara Brucker, Thomas Decker, Peter Fasching, Tanja Fehm, Wolfgang Janni, Sherko Kümmel, Andreas Schneeweiss, Martin Schuler, Diana Lüftner, Antonia Busse
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Summary:Background - 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. - Methods - 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. - Results - 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. - Conclusions - 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.
Item Description:First published: 23 December 2021
Gesehen am 21.07.2022
Physical Description:Online Resource
ISSN:1879-0852
DOI:10.1016/j.ejca.2021.11.025

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