PD-1/PD-L1 blockade inhibits epithelial-mesenchymal transition and improves chemotherapeutic response in breast cancer.

Abstract

Therapies targeting the PD-1/PD-L1 axis have recently been implemented for triple negative breast cancer (TNBC) management with limited efficacy, indicating that this axis may promote tumor growth by means other than immune suppression. Because PD-L1 overexpression causes resistance to the chemotherapeutic response in many cancers, here we explored the tumor promoting role of the PD-1/PD-L1 axis in breast cancer. We observed that the downregulation of PD-L1 by specific siRNA and pharmacological inhibitor significantly suppressed tumor cell proliferation, invasion and migration thereby enhancing T cell-mediated cell killing in vitro. We also showed that inhibiting PD-L1 improves cytotoxic sensitivity to chemotherapy in TNBC cells. Our in vivo results confirmed that combining a PD-L1 inhibitor with chemotherapy could significantly reduce tumor progression by inhibiting epithelial-mesenchymal transition. Overall, our results proved that PD-L1 contributes to the transformation and progression of breast cancer cells and that its intervention is a promising therapeutic strategy against breast cancer.