No patient left behind: The promise of immune priming with epigenetic agents.

No patient left behind: The promise of immune priming with epigenetic agents.

Oncoimmunology. 2017;6(10):e1315486

Authors: Carter CA, Oronsky BT, Roswarski J, Oronsky AL, Oronsky N, Scicinski J, Lybeck H, Kim MM, Lybeck M, Reid TR

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).

PMID: 29123948 [PubMed]

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