[Genome-Based Biomarkers of Immune Checkpoint Blockade Therapy]

Since 1981, cancer has been the leading cause of death in Japan, and its upward trend remains continuing until now. In 2013, approximately 365,000 Japanese died of cancer, and the ratio of the number of cancer-related deaths to the total number of deaths was 28.8%, implying that approximately 1 out of 3.5 deaths in Japan are caused by cancer. In recent years, immunotherapies are rapidly developed and recognized as an important anti-cancer treatment modality in addition to surgery, chemotherapy, and radiotherapy. In particular, the"immune checkpoint blockade therapy"has been attracting tremendous attention because of its potent clinical efficacy in the treatment of advanced cancers. The fundamental mechanism of the therapy is the induction of anti-tumor immune responses by disrupting the immunosuppressive mechanisms in the tumor milieu. Antibodies for the immune checkpoint blockade have been approved as clinical drugs in some countries, including in Japan, and a large number of clinical trials are currently in progress to further expand its application. However, several critical issues remain, one of which is the identification of biomarkers associated with clinical benefits or adverse events. In this review, we discuss recently reported genome-based biomarkers predictive for clinical benefits of immune checkpoint blockade therapies, namely activation of b-catenin signaling pathway and DNA mismatch repair deficiency.