No patient left behind: The promise of immune priming with epigenetic agents.
No patient left behind: The promise of immune priming with epigenetic agents.
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DOI：
10.1080/2162402x.2017.1315486
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发表时间：
2017
期刊：
影响因子：
7.2
通讯作者：
Reid TR
中科院分区：
文献类型：
--
作者：
Carter CA;Oronsky BT;Roswarski J;Oronsky AL;Oronsky N;Scicinski J;Lybeck H;Kim MM;Lybeck M;Reid TR
检查点抑制剂，抑制PD-1或CTLA-4的单克隆抗体，已经彻底改变了多种癌症的治疗。尽管人们对检查点抑制剂和免疫疗法的临床成功充满热情，但总的来说，只有少数特定肿瘤类型的患者实际上从治疗中受益。新出现的证据表明表观遗传学改变是免疫治疗临床耐药的一种机制。这篇综述提出了这种关联的证据，总结了肿瘤逃避免疫原性细胞死亡的表观机制，讨论了表观遗传调节作为一种综合策略的组成部分，以提高抗癌T细胞效应器功能与肿瘤免疫抑制周期的关系，最后，使这种无患者留守策略的成功关键取决于表观遗传剂的毒性特征。
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).