AUTHOR=Noessner Elfriede TITLE=DGK-α: A Checkpoint in Cancer-Mediated Immuno-Inhibition and Target for Immunotherapy JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=5 YEAR=2017 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2017.00016 DOI=10.3389/fcell.2017.00016 ISSN=2296-634X ABSTRACT=

Immunotherapy is moving to the forefront of cancer treatments owing to impressive durable responses achieved with checkpoint blockade antibodies and adoptive T-cell therapy. Still, improvements are necessary since, overall, only a small percentage of patients benefit from current therapies. Here, I summarize evidence that DGK-α may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytes in the tumor microenvironment. DGK-inhibitors can restore the antitumor function of tumor-suppressed adaptive and innate cytotoxic immunocytes. The activity of DGK-inhibitors lays downstream of current checkpoint blockade antibodies. Thus, synergistic effects are expected from combination strategies. Moreover, DGK-inhibitors may permit a double-strike attack on tumor cells as DGK-inhibition may not only re-instate immunological tumor attack but also may harm tumor cells directly by interfering with oncogenic survival pathways. Together, DGK-inhibitors have very promising characteristics and may be beneficially included into the armamentarium of cancer immunotherapeutics.