Abstract
This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane. Expression levels of PD-L1 and Gal-9 were evaluated and the activation status of NFκB in MDA-MB-231 and HS578T cells was determined to identify the PD-L1 and Gal-9 up-regulation mechanism. Three cases of increased PD-L1 expression and two of increased Gal-9 expression were observed among the TNBC patients. PD-L1 and Gal-9 expression were up-regulated by anthracycline and taxane in MDA-MB-231 cells, but not in HS578T cells. Increased nuclear levels of NFκB were observed in MDA-MB-231 cells treated with 0.5 μM epirubicin. Anthracycline and taxane up-regulated PD-L1 and Gal-9 expression in some subtypes of TNBC. This study provides useful reference data for clinical trials investigating combination treatments with immune checkpoint inhibitors and chemotherapy.
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