Baseline interleukin-6 is a prognostic factor for patients with metastatic breast cancer treated with eribulin

• Published in: Breast cancer research and treatment Vol. 202; no. 3; pp. 575 - 583
• Main Authors: Bun, Ayako, Nagahashi, Masayuki, Kuroiwa, Mamiko, Komatsu, Miki, Miyoshi, Yasuo
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.12.2023; Springer Nature B.V
• Subjects: Antitumor agents; Breast cancer; Cancer research; CD4 antigen; CD8 antigen; Cytokines; Cytotoxicity; Flow cytometry; Immunoregulation; Inflammation; Interleukin 6; Lymphocytes T; Medicine; Medicine & Public Health; Metastases; Metastasis; Microenvironments; Oncology; Original Laboratory Investigation; Serum levels; Suppressor cells; Tumors; Prognostic factor; Tumor immune microenvironment; Eribulin; Advanced breast cancer; Interleukin-6; Myeloid-derived suppressor cell
• ISSN: 0167-6806; 1573-7217
• DOI: 10.1007/s10549-023-07086-9

Purpose Eribulin is a unique anti-cancer drug which can improve overall survival (OS) of patients with metastatic breast cancer (MBC), probably by modulating the tumor immune microenvironment. The aim of this study was to investigate the clinical significance of serum levels of immune-related and inflammatory cytokines in patients treated with eribulin. Furthermore, we investigated the association between cytokines and immune cells, such as myeloid-derived suppressor cells (MDSCs) and cytotoxic and regulatory T cells, to explore how these cytokines might affect the immune microenvironment. Methods Sixty-eight patients with MBC treated with eribulin were recruited for this retrospective study. The relationship of cytokines, including interleukin (IL)-6, to progression-free survival and OS was examined. CD4 +  and CD8 +  lymphocyte, MDSCs and regulatory T cell levels were determined in the blood by flow cytometry analysis. Results In our cohort, patients with high IL-6 at baseline had shorter progression-free survival and OS compared with those with low IL-6 ( p  = 0.0017 and p  = 0.0012, respectively). Univariable and multivariable analyses revealed that baseline IL-6 was an independent prognostic factor for OS ( p  = 0.0058). Importantly, CD8 +  lymphocytes were significantly lower and MDSCs were significantly higher in patients with high IL-6, compared to those with low IL-6. Conclusion Baseline IL-6 is an important prognostic factor in patients with MBC treated with eribulin. Our results show that high IL-6 is associated with higher levels of MDSCs which suppress anti-tumor immunity, such as CD8 +  cells. It appears that eribulin is not particularly effective in patients with high IL-6 due to a poor tumor immune microenvironment.