Epigenetic modulation of antitumor immunity for improved cancer immunotherapy.
Epigenetic modulation of antitumor immunity for improved cancer immunotherapy.
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DOI：
10.1186/s12943-021-01464-x
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发表时间：
2021-12-20
期刊：
影响因子：
37.3
通讯作者：
Guo ZS
中科院分区：
文献类型：
--
作者：
Dai E;Zhu Z;Wahed S;Qu Z;Storkus WJ;Guo ZS
表观遗传机制不仅在癌症的发生和进展中发挥着重要作用，而且在免疫细胞的激活、分化和效应功能中也发挥着重要作用。在这篇综述中，我们总结了与影响免疫细胞命运和功能的免疫细胞表观基因组动力学以及癌细胞的免疫原性相关的当前文献。一些重要的免疫相关基因，如颗粒酶 B、IFN-γ、IL-2、IL-12、FoxP3 和 STING，通过免疫或/和癌细胞中的表观遗传机制进行调节，免疫细胞和肿瘤相关基质细胞表达的免疫检查点分子（PD-1、CTLA-4、TIM-3、LAG-3、TIGIT）也是如此。因此，表观遗传调节药物的治疗策略预计将通过促进局部免疫细胞群的转录和代谢重编程来显着影响肿瘤微环境（TME），从而抑制免疫抑制细胞（MDSC和Treg）并激活抗肿瘤T效应细胞、专业抗原呈递细胞（APC）以及可充当非专业APC的癌细胞。在后一种情况下，表观遗传调节剂可以通过诱导转录抑制的肿瘤相关抗原的从头表达、增加新抗原和MHC加工/呈递机制的表达以及激活肿瘤免疫原性细胞死亡（ICD）来协调促进肿瘤免疫原性。 ICD 为抗肿瘤 T 细胞交叉启动和使癌细胞对介入免疫治疗敏感提供了丰富的免疫原来源。通过这种方式，表观遗传调节剂可以被设想为能够介导卓越治疗功效的联合免疫治疗方法中的有效成分。
Epigenetic mechanisms play vital roles not only in cancer initiation and progression, but also in the activation, differentiation and effector function(s) of immune cells. In this review, we summarize current literature related to epigenomic dynamics in immune cells impacting immune cell fate and functionality, and the immunogenicity of cancer cells. Some important immune-associated genes, such as granzyme B, IFN-γ, IL-2, IL-12, FoxP3 and STING, are regulated via epigenetic mechanisms in immune or/and cancer cells, as are immune checkpoint molecules (PD-1, CTLA-4, TIM-3, LAG-3, TIGIT) expressed by immune cells and tumor-associated stromal cells. Thus, therapeutic strategies implementing epigenetic modulating drugs are expected to significantly impact the tumor microenvironment (TME) by promoting transcriptional and metabolic reprogramming in local immune cell populations, resulting in inhibition of immunosuppressive cells (MDSCs and Treg) and the activation of anti-tumor T effector cells, professional antigen presenting cells (APC), as well as cancer cells which can serve as non-professional APC. In the latter instance, epigenetic modulating agents may coordinately promote tumor immunogenicity by inducing de novo expression of transcriptionally repressed tumor-associated antigens, increasing expression of neoantigens and MHC processing/presentation machinery, and activating tumor immunogenic cell death (ICD). ICD provides a rich source of immunogens for anti-tumor T cell cross-priming and sensitizing cancer cells to interventional immunotherapy. In this way, epigenetic modulators may be envisioned as effective components in combination immunotherapy approaches capable of mediating superior therapeutic efficacy.
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影响因子：
15.9
作者：
Berglund, Anders;Mills, Matthew;Kim, Sungjune
通讯作者：
Kim, Sungjune
DNMT和HDAC抑制剂诱导长时间重复序列编码的隐秘转录起始位点。
影响因子：
30.8
作者：
Brocks D;Schmidt CR;Daskalakis M;Jang HS;Shah NM;Li D;Li J;Zhang B;Hou Y;Laudato S;Lipka DB;Schott J;Bierhoff H;Assenov Y;Helf M;Ressnerova A;Islam MS;Lindroth AM;Haas S;Essers M;Imbusch CD;Brors B;Oehme I;Witt O;Lübbert M;Mallm JP;Rippe K;Will R;Weichenhan D;Stoecklin G;Gerhäuser C;Oakes CC;Wang T;Plass C
通讯作者：
Plass C
DOI：
10.1038/s41573-020-00108-x
发表时间：
2021-04
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
Bhat KP;Ümit Kaniskan H;Jin J;Gozani O
通讯作者：
Gozani O
影响因子：
16.6
作者：
An J;González-Avalos E;Chawla A;Jeong M;López-Moyado IF;Li W;Goodell MA;Chavez L;Ko M;Rao A
通讯作者：
Rao A
组蛋白 H3.3 磷酸化会放大刺激诱导的转录。
影响因子：
64.8
作者：
Armache A;Yang S;Martínez de Paz A;Robbins LE;Durmaz C;Cheong JQ;Ravishankar A;Daman AW;Ahimovic DJ;Klevorn T;Yue Y;Arslan T;Lin S;Panchenko T;Hrit J;Wang M;Thudium S;Garcia BA;Korb E;Armache KJ;Rothbart SB;Hake SB;Allis CD;Li H;Josefowicz SZ
通讯作者：
Josefowicz SZ