No patient left behind: The promise of immune priming with epigenetic agents. (3rd October 2017)

• Record Type: Journal Article
• Authors: Carter, Corey A.; Oronsky, Bryan T.; Roswarski, Joseph; Oronsky, Arnold L.; Oronsky, Neil; Scicinski, Jan; Lybeck, Harry; Kim, Michelle M.; Lybeck, Michelle; Reid, Tony R.
• Is Part Of: Oncoimmunology. Volume 6:Number 10(2017)
• Publication Date: 2017-10-03
• Subjects: Immunotherapy -- immunosuppression -- immunogenic cell death -- epigenetic modulation -- checkpoint inhibitors -- resistance; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2017.1315486
• Languages: English
• ISSNs: 2162-402X

Abstract

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).