| Autor: |
Carter CA; Walter Reed National Military Medical Center, Murtha Cancer Center, Bethesda, MD, USA., Oronsky BT; EpicentRx, Inc., San Diego, CA, USA., Roswarski J; Walter Reed National Military Medical Center, Murtha Cancer Center, Bethesda, MD, USA., Oronsky AL; InterWest Partners, Menlo Park, CA, USA., Oronsky N; CFLS Data, San Jose, CA, USA., Scicinski J; EpicentRx, Inc., San Diego, CA, USA., Lybeck H; University of Helsinki, Department of Physiology, Helsinki, Finland., Kim MM; University of Michigan, Department of Radiation Oncology, Ann Arbor, MI, USA., Lybeck M; EpicentRx, Inc., San Diego, CA, USA., Reid TR; University of California San Diego, Moores Cancer Center, La Jolla, CA, USA. |
| Abstrakt: |
Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as a component of an integrated strategy to boost anticancer T cell effector function in relation to a tumor immunosuppression cycle and, finally, makes the case that the success of this no-patient-left-behind strategy critically depends on the toxicity profile of the epigenetic agent(s). |
