Abstract
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).
Original language | English (US) |
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Article number | e1315486 |
Journal | OncoImmunology |
Volume | 6 |
Issue number | 10 |
DOIs | |
State | Published - Oct 3 2017 |
Keywords
- Immunotherapy
- checkpoint inhibitors
- epigenetic modulation
- immunogenic cell death
- immunosuppression
- resistance
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Oncology