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

Item Type:Article
Title:Treatment with ribociclib shows favourable immunomodulatory effects in patients with hormone receptor-positive breast cancer-findings from the RIBECCA trial
Creators Name:Peuker, C.A. and Yaghobramzi, S. and Grunert, C. and Keilholz, L and Gjerga, E. and Hennig, S. and Schaper, S. and Na, I.K. and Keller, U. and Brucker, S. and Decker, T. and Fasching, P. and Fehm, T. and Janni, W. and Kümmel, S. and Schneeweiss, A. and Schuler, M. and Lüftner, D. and Busse, A.
Abstract: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.
Keywords:CDK4/6 Inhibitors, Ribociclib, Breast Cancer, Immunomodulation, Adaptive Immunity
Source:European Journal of Cancer
ISSN:0959-8049
Publisher:Elsevier
Volume:162
Page Range:45-55
Date:February 2022
Official Publication:https://doi.org/10.1016/j.ejca.2021.11.025
PubMed:View item in PubMed

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