DGK-α: A Checkpoint in Cancer-Mediated Immuno-Inhibition and Target for Immunotherapy.
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.
Immunoanalytics Core Facility and Research Group Tissue Control of Immunocytes, Helmholtz Zentrum München München, Germany.
Elfriede
E
Noessner
anergy; diacylglycerol kinase; human tumor; immunotherapy; renal cell carcinoma; tumor-infiltrating lymphocytes