PD-1/PD-L1 blockage in cancer treatment—from basic research to clinical application

Excerpt

For several decades, the primary medical treatment for solid malignant tumors, including ovarian cancer, has been cytotoxic “chemotherapy”. However, novel drugs are drastically changing cancer treatment. Among them, the newest and most promising modality is emerging in the field of cancer immunotherapy. Although immune-based cancer treatment has long been investigated, only recently has its clinical efficacy equaled or surpassed conventional chemotherapy. This striking effect of novel immune therapy has been achieved by drugs called “immune checkpoint inhibitors”, especially antibodies to block the PD-L1/PD-1 (programmed cell death ligand-1/programmed cell death-1) immune signal. PD-1 was originally identified by Ishida et al., and subsequently found to have essential roles in the regulation of various immune reactions including host–tumor immunity [1]. Two ligands for PD-1, PD-L1 and PD-L2, were identified [2, 3]. Expression of PD-L1 in cancer cells and the immune inhibitory signal via PD-1 on immune cells have been implicated in the clinical course of cancer patients with various tumors [4]. Moreover, an increasing number of reports have uncovered the clinical benefit of immune therapies targeting the PD-L1/PD-1 signal and are altering cancer treatment [5‐7]. …