Borcoman Edith, Kamal Maud, Marret Grégoire, Dupain Celia, Castel-Ajgal Zahra, Le Tourneau Christophe
Department of Drug Development and Innovation (D3i), Institut Curie, 75005 Paris, France.
INSERM U900 Research Unit, 92210 Saint-Cloud, France.
Cancers (Basel). 2021 Dec 23;14(1):66. doi: 10.3390/cancers14010066.
Immunotherapy has made a breakthrough in medical oncology with the approval of several immune checkpoint inhibitors in clinical routine, improving overall survival of advanced cancer patients with refractory disease. However only a minority of patients experience a durable response with these agents, which has led to the development of combination strategies and novel immunotherapy drugs to further counteract tumor immune escape. Epigenetic regulations can be altered in oncogenesis, favoring tumor progression. The development of epidrugs has allowed targeting successfully these altered epigenetic patterns in lymphoma and leukemia patients. It has been recently shown that epigenetic alterations can also play a key role in tumor immune escape. Epidrugs, like HDAC inhibitors, can prime the anti-tumor immune response, therefore constituting interesting partners to develop combination strategies with immunotherapy agents. In this review, we will discuss epigenetic regulations involved in oncogenesis and immune escape and describe the clinical development of combining HDAC inhibitors with immunotherapies.
随着几种免疫检查点抑制剂在临床常规中获得批准，免疫疗法在医学肿瘤学领域取得了突破，提高了患有难治性疾病的晚期癌症患者的总生存率。然而，只有少数患者对这些药物有持久反应，这导致了联合策略和新型免疫疗法药物的开发，以进一步对抗肿瘤免疫逃逸。表观遗传调控在肿瘤发生过程中可能会发生改变，从而促进肿瘤进展。表观遗传药物的开发使得在淋巴瘤和白血病患者中成功靶向这些改变的表观遗传模式成为可能。最近有研究表明，表观遗传改变在肿瘤免疫逃逸中也可能起关键作用。表观遗传药物，如组蛋白去乙酰化酶（HDAC）抑制剂，可以启动抗肿瘤免疫反应，因此构成了与免疫治疗药物开发联合策略的有趣伙伴。在这篇综述中，我们将讨论参与肿瘤发生和免疫逃逸的表观遗传调控，并描述HDAC抑制剂与免疫疗法联合应用的临床进展。
