Epigenetic modulation of immunotherapy and implications in head and neck cancer.
Epigenetic modulation of immunotherapy and implications in head and neck cancer.
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DOI：
10.1007/s10555-020-09944-0
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Uppaluri R
中科院分区：
文献类型：
--
作者：
Zhou L;Xu N;Shibata H;Saloura V;Uppaluri R
癌细胞为了避免免疫识别和清除而开发的不同机制促进了癌症的进展。通过阻断PD-1/PD-L1和CTLA4的单抗，免疫检查点阻断(ICB)在各种癌症类型中的临床应用取得了良好的持久疗效，包括复发和转移性头颈部鳞状细胞癌(HNSCC)。HNSCC是ICB治疗的合理靶点，因为它的突变负荷相对较高，且存在免疫渗透。然而，有限的应答率和最近的阴性临床试验数据表明，迫切需要新的战略来克服免疫治疗耐药性。临床前研究揭示了表观遗传调节因子在抗肿瘤免疫反应中的重要作用。肿瘤和宿主免疫系统相互作用的多个组成部分处于表观遗传调控之下，包括癌细胞本身、细胞毒性T淋巴细胞、调节性T淋巴细胞、自然杀伤细胞和肿瘤相关巨噬细胞。表观遗传靶向药物，如DNA甲基转移酶抑制剂、组蛋白脱乙酰酶和甲基转移酶抑制剂，已经证明在各种癌症模型中具有逆转免疫抑制的潜力。这篇综述的目的是总结最近的临床前研究，重点是研究表观遗传调节在宿主免疫和癌细胞界面中的功能。我们还提出了在HNSCC的管理中结合表观遗传调节和免疫治疗以改善结果的观点--这是未来临床研究中非常感兴趣的领域。
Cancer progression is facilitated by distinct mechanisms developed by cancer cells to avoid immune recognition and clearance. The clinical application of immune checkpoint blockade (ICB), via monoclonal antibodies blocking PD-1/PD-L1 and CTLA4, has achieved promising durable therapeutic response in various cancer types, including recurrent and metastatic head and neck squamous cell carcinomas (HNSCC). HNSCC represents a rational target of ICB treatment given its relatively high mutation burden and the presence of immune infiltrates. However, the limited response rates and recent negative clinical trials data identify an urgent need for new strategies to overcome immunotherapy resistance. Preclinical studies have revealed an important contribution of epigenetic regulators in the anti-tumor immune response. Multiple components of the tumor and host immune system interaction are under epigenetic regulation, including the cancer cells themselves, cytotoxic T lymphocytes, regulatory T lymphocytes, natural killer cells, and tumor-associated macrophages. Epigenetic targeting drugs such as DNA methyltransferase inhibitors, histone deacetylase, and methyltransferase inhibitors have demonstrated the potential to reverse immune suppression in various cancer models. The aim of this review is to summarize recent preclinical studies focused on investigating the function of epigenetic modulation in the host immune and cancer cell interface. We also provide a perspective on combining epigenetic modulation and immunotherapy in the management of HNSCC to improve outcomes—an area of great interest in future clinical studies.
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