PD-1/PD-L1 blockade in cancer treatment: perspectives and issues

• Published in: International journal of clinical oncology Vol. 21; no. 3; pp. 462 - 473
• Main Authors: Hamanishi, Junzo, Mandai, Masaki, Matsumura, Noriomi, Abiko, Kaoru, Baba, Tsukasa, Konishi, Ikuo
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.06.2016; Springer Nature B.V
• Subjects: Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; B7-H1 Antigen - antagonists & inhibitors; Biomarkers; Biomarkers, Tumor; Cancer; Cancer Research; Clinical trials; Clinical Trials as Topic; Humans; Immunotherapy; Invited Review; Invited Review Article; Medicine; Medicine & Public Health; Neoplasms - therapy; Oncology; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Protein expression; Surgical Oncology; T-Lymphocytes - immunology; Tumor Escape - immunology; Tumor Microenvironment - immunology; PD-L1; Value; Biomarker; PD-1; Nivolumab; Immunotherapy
• ISSN: 1341-9625; 1437-7772
• DOI: 10.1007/s10147-016-0959-z

Recent studies showed that tumor cells ‘edit’ host immunity in several ways to evade immune defenses in the tumor microenvironment. This phenomenon is called “cancer immune escape.” One of the most important components in this system is an immunosuppressive co-signal (immune checkpoint) mediated by the PD-1 receptor and its ligand, PD-L1. PD-1 is mainly expressed on activated T cells, whereas PD-L1 is expressed on several types of tumor cells. Preclinical studies have shown that inhibition of the interaction between PD-1 and PD-L1 enhances the T-cell response and mediates antitumor activity. Several clinical trials of PD-1/PD-L1 signal-blockade agents have exhibited dramatic antitumor efficacy in patients with certain types of solid or hematological malignancies. In this review, we highlight recent clinical trials using anti-PD-1 or anti-PD-L1 antibodies against several types of malignancies, including a trial conducted in our department, and describe the clinical perspectives and issues regarding the PD-1/PD-L1 blockade in cancer treatment.