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| 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: |
Peuker, C.A.  ORCID: https://orcid.org/0000-0002-0957-2166, Yaghobramzi, S., Grunert, C. ORCID: https://orcid.org/0000-0001-8376-8629, Keilholz, L, Gjerga, E., Hennig, S., Schaper, S., Na, I.K. ORCID: https://orcid.org/0000-0001-9902-5424, Keller, U. ORCID: https://orcid.org/0000-0002-8485-1958, Brucker, S. ORCID: https://orcid.org/0000-0001-5162-1542, Decker, T., Fasching, P., Fehm, T., Janni, W., Kümmel, S. ORCID: https://orcid.org/0000-0001-9355-494X, Schneeweiss, A., Schuler, M. ORCID: https://orcid.org/0000-0002-2166-3394, Lüftner, D. ORCID: https://orcid.org/0000-0003-2511-9115 and Busse, A. ORCID: https://orcid.org/0000-0002-3470-6947
|
| 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 |
| Additional Information: | Copyright © 2021 Elsevier Ltd. All rights reserved. This manuscript version is made available under the Creative Commons Attribution-NonCommercialNoDerivatives 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ or send a letter to Creative Commons, PO Box 1866, Mountain View, CA 94042, USA. |
| Official Publication: | https://doi.org/10.1016/j.ejca.2021.11.025 |
| PubMed: | View item in PubMed |
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