LEADING ARTICLE Clinical Impact of Checkpoint Inhibitors as Novel Cancer Therapies

The Author(s) 2014. This article is published with open access at Springerlink.com Abstract Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibi-tory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing under-standing of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhib-itory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among the first to be tested in the clinic, and ipi-limumab was the first immune checkpoint inhibitor approved for an anticancer indication. Agents targeting th