期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 5, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2017.00016
关键词
tumor-infiltrating lymphocytes; renal cell carcinoma; diacylglycerol kinase; immunotherapy; anergy; human tumor
资金
- Deutsche Forschungsgemeinschaft [SFB-TR36]
- Deutsche Krebshilfe [110370]
- Erich und Gertrud von Roggenbuck Stiftung [218-15]
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-alpha may represent an immunological checkpoint suppressing the activity of cytotoxic immunocytec 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.
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