Eribulin is an immune potentiator in breast cancer that upregulates human leukocyte antigen class I expression via the induction of NOD‐like receptor family CARD domain‐containing 5

Abstract

AbstractEribulin inhibits microtubule polymerization and improves the overall survival of patients with recurrent metastatic breast cancer. A subgroup analysis revealed a low neutrophil to lymphocyte ratio (NLR) (<3) to be a prognostic factor of eribulin treatment. We thus hypothesized that eribulin might be related to the immune response for breast cancer cells and we analyzed the effects of eribulin on the immune system. Immunohistochemical staining revealed that human leukocyte antigen (HLA) class I expression was increased in clinical samples after eribulin treatment. In vitro assays revealed that eribulin treatment increased HLA class I expression in breast cancer line cells. RNA‐sequencing demonstrated that eribulin treatment increased the expression of the NOD‐like family CARD domain‐containing 5 (NLRC5), a master regulator of HLA class I expression. Eribulin treatment increased the NY‐ESO‐1‐specific T‐cell receptor (TCR) transduced T (TCR‐T) cell response for New York oesophageal squamous cell carcinoma 1 (NY‐ESO‐1) overexpressed breast cancer cells. The eribulin and TCR‐T combined therapy model revealed that eribulin and immunotherapy using TCR‐T cells has a synergistic effect. In summary, eribulin increases the expression of HLA class 1 via HLA class 1 transactivatior NLRC5 and eribulin combination with immunotherapy can be effective for the treatment of breast cancer.