Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Wimmer, K; Sachet, M; Ramos, C; Frantal, S; Birnleitner, H; Brostjan, C; Exner, R; Filipits, M; Bago-Horvath, Z; Rudas, M; Bartsch, R; Gnant, M; Singer, CF; Balic, M; Egle, D; Oehler, R; Fitzal, F.
Differential immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel in breast cancer patients.
J Exp Clin Cancer Res. 2023; 42(1):300
Doi: 10.1186/s13046-023-02876-x
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- Co-Autor*innen der Med Uni Graz
- Balic Marija
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- Abstract:
- BACKGROUND: Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect on lymphocytes may depend on the chemotherapy backbone. Therefore, we separately compared the immunomodulatory effects of EC and D in the setting of a randomized clinical trial. METHODS: Tumor and blood samples of 154 patients from the ABCSG-34 trial were available (76 patients received four cycles of EC followed by four cycles of D; 78 patients get the reverse treatment sequence). Tumor-infiltrating lymphocytes, circulating lymphocytes and 14 soluble immune mediators were determined at baseline and at drug change. Furthermore, six BC cell lines were treated with E, C or D and co-cultured with immune cells. RESULTS: Initial treatment with four cycles of EC reduced circulating B and T cells by 94% and 45%, respectively. In contrast, no comparable effects on lymphocytes were observed in patients treated with initial four cycles of D. Most immune mediators decreased under EC whereas D-treatment resulted in elevated levels of CXCL10, urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR). Accordingly, only the exposure of BC cell lines to D induced similar increases as compared to E. While treatment of BC cells with E was associated with cell shrinkage and apoptosis, D induced cell swelling and accumulation of cells in G2 phase. CONCLUSION: The deleterious effect of EC on lymphocytes indicates strong immunosuppressive properties of this combination therapy. D, in contrast, has no effect on lymphocytes, but triggers the secretion of stimulatory proteins in vivo and in vitro, indicating a supportive effect on the immune system. Underlying differences in the induced cell death might be causal. These divergent immunomodulatory effects of epirubicin/cyclophosphamide and docetaxel should be considered when planning future combinations with immunotherapies in breast cancer.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Female - administration & dosage
- Breast Neoplasms - pathology
- Docetaxel - therapeutic use
- Epirubicin - adverse effects
- Cyclophosphamide - pharmacology
- Taxoids - pharmacology
- Neoadjuvant Therapy - methods
- Antineoplastic Combined Chemotherapy Protocols - pharmacology, therapeutic use
- Treatment Outcome - administration & dosage
- Fluorouracil - administration & dosage
- Find related publications in this database (Keywords)
- Neoadjuvant chemotherapy
- Breast cancer
- Immune cells
- Epirubicin
- Docetaxel
- Immunomodulatory markers
- Prediction of response to chemotherapy