Combinatorial Strategies With PD-1/PD-L1 Immune Checkpoint Blockade for Breast Cancer Therapy: Mechanisms and Clinical Outcomes

Abstract

As an emerging antitumor strategy, immune checkpoint therapy is one of the most promising anticancer therapies due to its long response duration. Antibodies against the programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) axis have been extensively applied to various cancers and have demonstrated unprecedented efficacy. Nevertheless, a poor response to monotherapy with anti-PD-1/PD-L1 has been observed in metastatic breast cancer. Combination therapy with other standard treatments is expected to overcome this limitation of PD-1/PD-L1 blockade in the treatment of breast cancer. In the present review, we first illustrate the biological functions of PD-1/PD-L1 and their role in maintaining immune homeostasis as well as protecting against immune-mediated tissue damage in a variety of microenvironments. Several combination therapy strategies for the combination of PD-1/PD-L1 blockade with standard treatment modalities have been proposed to solve the limitations of anti-PD-1/PD-L1 treatment, including chemotherapy, radiotherapy, targeted therapy, antiangiogenic therapy, and other immunotherapies. The corresponding clinical trials provide valuable estimates of treatment effects. Notably, several combination options significantly improve the response and efficacy of PD-1/PD-L1 blockade. This review provides a PD-1/PD-L1 clinical trial landscape survey in breast cancer to guide the development of more effective and less toxic combination therapies.

Keywords: adverse events; anti-PD-1/PD-L1; biomarkers; chemotherapy; combination therapy; irradiation; targeted therapy.