<scp>PD</scp>‐1 as a potential target in cancer therapy

<jats:title>Abstract</jats:title><jats:p>Recently, an improved understanding of the molecular mechanisms governing the host response to tumors has led to the identification of checkpoint signaling pathways involved in limiting the anticancer immune response. One of the most critical checkpoint pathways responsible for mediating tumor‐induced immune suppression is the programmed death‐1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐1) pathway, normally involved in promoting tolerance and preventing tissue damage in settings of chronic inflammation. Many human solid tumors express <jats:styled-content style="fixed-case">PD</jats:styled-content> ligand 1 (<jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1), and this is often associated with a worse prognosis. Tumor‐infiltrating lymphocytes from patients with cancer typically express <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 and have impaired antitumor functionality. Proof‐of‐concept has come from several preclinical studies in which blockade of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 or <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 enhanced T‐cell function and tumor cell lysis. Three monoclonal antibodies against <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1, and one against <jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1, have reported phase 1 data. All four agents have shown encouraging preliminary activity, and those that have been evaluated in larger patient populations appear to have encouraging safety profiles. Additional data are eagerly awaited. This review summarizes emerging clinical data and potential of <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1 pathway–targeted antibodies in development. If subsequent investigations confirm the initial results, it is conceivable that agents blocking the <jats:styled-content style="fixed-case">PD</jats:styled-content>‐1/<jats:styled-content style="fixed-case">PD</jats:styled-content>‐L1 pathway will prove valuable additions to the growing armamentarium of targeted immunotherapeutic agents.</jats:p>