Impact of cytotoxic treatments on PD-L1 expression in human breast cancer cell lines
20 September 2018 (online)
The oncologic spectrum for the clinical utilization of checkpoint inhibitors (CI) expands rapidly. Clinical trials with CI in breast cancer (BC) report an overall response rate of up to 19% with durable clinical responses and tolerable safety profiles. Improved understanding of the immunogenicity of BC under simultaneously applied therapies, e.g., cytotoxic treatments, would help to develop more individual therapeutic strategies to further increase response rates.
We investigated the expression of PD-L1 on different types (triple negative, luminal-type and HER2-positive) of human BC cell lines and evaluated the effect of standard chemotherapeutical agents (epirubicin and paclitaxel) on PD-L1 expression in selected cell lines.
We found greatly varying levels of PD-L1 expression within the investigated BC cell lines. High PD-L1 expression was found in all three TNBC- and two of three HER2-overexpressing cell lines. Luminal like tumors seem to express low PD-L1 levels, without great variations. Epirubicin treatment caused a decrease and paclitaxel treatment an increase in PD-L1 expression in the TNBC MDA-MB-231 cells. In contrast, PD-L1 expression changed to a minor extent in the HER2-overexpressing SK-BR-3 cell line when exposed to cytotoxic treatments.
The degree of PD-L1 expression among breast cancer cell lines varies considerably. Our analyses revealed different cell type specific responses to cytotoxic treatments. Furthermore, diverse chemotherapeutic agents engender dissimilar PD-L1 expression changes within the same cell line, which likely contribute to the varying clinical responses to CI. Further studies are needed to identify the major mechanisms determining the immunogenic alterations of BC under chemotherapy.