Abstract 4996: Analysis of the effect of eribulin on tumor immunity against triple-negative breast cancer
Authors: Tadafumi Shimizu , Oba Takaaki , Ito Ken-ichi 
Published: March 2024

Purpose: Chemotherapeutic agents may induce immunomodulatory effects on immune cells and cancer cells in patients with triple negative breast cancer (TNBC). Recent studies have demonstrated that absolute lymphocyte count in peripheral blood can predict response to eribulin in patients with breast cancer, suggesting that eribulin have some favorable effects on immune cells. However, there have been no reports demonstrating the mechanisms of how eribulin affects the immune cells of patients with breast cancer. This study aimed to analyze the effect of eribulin on T cells in vitro and in vivo.

Materials & Methods: Using human peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with TNBC, we investigated the effects of eribulin on proliferation of these cells, changes in the expression of surface markers, and antitumor effects on TNBC cells. Three TNBC cell lines (MDA-MB-231, Hs578T, MDA-MB-157) were used in this study. Human PBMCs were activated by CD3/CD28 stimulation in vitro for six days and analyzed for T-cell surface markers by flow cytometry. For three patients with TNBC who underwent eribulin treatment, blood was collected at baseline and on days 8, 22, and 64 after treatment, and PBMCs were isolated, and analyzed by flow cytometry.

Results: The proliferation of activated CD8+ T cells from healthy donors and patients was facilitated when cultured with 1nM of eribulin compared to the control. Moreover, eribulin significantly decreased CD4/8 ratio in T cells (p&lt; 0.05). In PBMCs from healthy donors, the frequency of CD45RA+ CD45RO- cells and CCR7+ cells in CD8+ T cells was significantly increased by eribulin treatment (p&lt; 0.05). Furthermore, eribulin significantly increased CD127+ KLRG1- cells (memory precursor effector cells) and TCF1+ cells in CD8+ T cells (p&lt; 0.01). Furthermore, the anti-tumor effect of activated T cells from PBMCs of healthy donors and patients with TNBC was enhanced when cultured with eribulin in all three TNBC cell lines compared to control, and IFNγ+ CD8+ T cells were significantly increased by eribulin treatment (p&lt; 0.05). However, in TNBC patients treated with eribulin in clinical practice, there were no significant changes in the CD4/8 ratio, the frequency of CD45RA+ cells or CCR7+ cells in CD8+ T cells before and after treatment of eribulin.

Conclusions: Our findings suggest that eribulin can facilitate the proliferation of CD8+ T cells and potentiates T cell-mediated anti-tumor activity against triple-negative breast cancer cells in vitro. Further analysis of the effects of eribulin on TNBC cells and immune cells in vivo is required, and we continue to analyze immunomodulation in patients treated with eribulin.

Citation Format: Shimizu Tadafumi, Takaaki Oba, Ken-ichi Ito. Analysis of the effect of eribulin on tumor immunity against triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4996.