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Eribulin promotes proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells

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Abstract

Purpose

Chemotherapeutic agents exert immunomodulatory effects on triple-negative breast cancer (TNBC) cells and immune cells. Eribulin favorably affects the immunological status of patients with breast cancer. However, the effects of eribulin on the immune cells remain unexplored. The aim of this study was to investigate the effects of eribulin on immune cells.

Methods

Peripheral blood mononuclear cells (PBMCs) from healthy donors and mouse splenocytes were stimulated with anti-CD3 and anti-CD28 antibodies. The effects of eribulin and paclitaxel on cell proliferation and differentiation status were analyzed using flow cytometry. RNA sequencing was performed to assess alterations in gene expression in CD8+ T cells following eribulin and paclitaxel treatment. Using TNBC cell lines (MDA-MB-231, Hs578T, and MDA-MB-157), the anti-tumor activity of CD3/CD28-stimulated T cells combined with eribulin or paclitaxel was evaluated.

Results

Eribulin did not affect CD3/CD28-stimulated PBMCs proliferation. However, eribulin significantly decreased the CD4/CD8 ratio in T cells, indicating that eribulin facilitates CD8+ T cell proliferation. Furthermore, eribulin significantly increased the frequency of less differentiated CD45RA+, CCR7+, and TCF1+ subsets of CD8+ T cells. RNA sequencing revealed that eribulin enhanced the expression of gene sets related to cell proliferation and immune responses. Moreover, eribulin augmented the anti-tumor effects of CD3/CD28-stimulated T cells against TNBC cells. These results were not observed in experiments using paclitaxel.

Conclusions

Eribulin promoted CD8+ T cell proliferation, repressed effector T cell differentiation, and harnessed T cell-mediated anti-tumor effects. These mechanisms may be one of the cues that eribulin can improve the immunological status of tumor-bearing hosts.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by Grants-in-aid for Scientific Research from the Japanese Society for the Promotion of Science (#21K15529), YOKOYAMA Foundation for Clinical Pharmacology (YRY-2101), Takeda Science Foundation, and Shinshu Public Utility Foundation for Promotion of Medical Sciences.

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Authors and Affiliations

  1. Division of Breast and Endocrine Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-861, Japan

    Tadafumi Shimizu, Takaaki Oba & Ken-ichi Ito

  2. Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan

    Masanori Oshi

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  1. Tadafumi Shimizu
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  2. Takaaki Oba
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Correspondence to Takaaki Oba.

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This study was approved by the Medical Ethics Committee on Clinical Investigation of Shinshu University (No. 730 and No. 3819). All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Shimizu, T., Oba, T., Oshi, M. et al. Eribulin promotes proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells. Breast Cancer Res Treat 203, 57–71 (2024). https://doi.org/10.1007/s10549-023-07111-x

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