Eribulin represses effector T cell differentiation and enhances T cell-mediated anti-tumor activity to triple negative breast cancer cells through the facilitation of CD8+ T cell proliferation

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 antitumor 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 antitumor effects. These mechanisms may be one of the cues that eribulin can improve the immunological status of tumor-bearing hosts.