放疗后肿瘤细胞引起的炎症性微环境重塑（Nat Rev Cancer, IF: 51）

0328 来自SCI天天读 00:00 01:59

SCI

28 Mar 2020

Inflammatory microenvironment remodelling by tumour cells after radiotherapy

• McLaughlin M, Patin EC, Pedersen M, et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy. Nat Rev Cancer 2020.

• Martin McLaughlin, Targeted Therapy Team, The Institute of Cancer Research, London, UK; e- mail: martin.mclaughlin@ icr.ac.uk

The development of immune checkpoint inhibitors (ICIs) is revolutionizing the way we think about cancer treatment. Even so, for most types of cancer, only a minority of patients currently benefit from ICI therapies. Intrinsic and acquired resistance to ICIs has focused research towards new combination therapy approaches that seek to increase response rates, the depth of remission and the durability of benefit. In this Review, we describe how radiotherapy, through its immunomodulating effects, represents a promising combination partner with ICIs. We describe how recent research on DNA damage response (DDR) inhibitors in combination with radiotherapy may be used to augment this approach. Radiotherapy can kill cancer cells while simultaneously triggering the release of pro- inflammatory mediators and increasing tumour- infiltrating immune cells – phenomena often described colloquially as turning immunologically ‘cold’ tumours ‘hot’. Here, we focus on new developments illustrating the key role of tumour cell- autonomous signalling after radiotherapy. Radiotherapy- induced tumour cell micronuclei activate cytosolic nucleic acid sensor pathways, such as cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING), and propagation of the resulting inflammatory signals remodels the immune contexture of the tumour microenvironment. In parallel, radiation can impact immunosurveillance by modulating neoantigen expression. Finally, we highlight how tumour cell- autonomous mechanisms might be exploited by combining DDR inhibitors, ICIs and radiotherapy.

免疫检查点抑制剂（ICIs）的发展正在彻底改变我们看待癌症治疗的看法。即便如此，对于大多数类型的癌症，目前只有少数患者受益于ICI治疗。对ICIs的内在和获得性抵抗已将研究集中于寻求新的联合疗法方法，以寻求提高应答率、缓解深度和获益的持久性。在本综述中，我们描述了放射疗法如何通过其免疫调节作用，代表一个ICI的有希望的联合治疗伙伴。我们描述了如何结合放疗对DNA损伤反应（DDR）抑制剂的最新研究可用于增强这种方法。放射治疗可以杀死癌细胞，同时触发促炎性介质的释放，并增加肿瘤浸润免疫细胞，这种现象通常被俗称为免疫“冷”肿瘤“变热”。在这里，我们关注于新的发展，将重点介绍放射治疗后肿瘤细胞自主信号的关键作用。放疗诱导的肿瘤细胞微核激活了胞质核酸传感通路，如环GMP-AMP合酶（cGAS）-干扰素基因刺激因子（STING），由此产生的炎症信号的传播重塑了肿瘤微环境的免疫环境。同时，辐射可以通过调节新抗原的表达来影响免疫监测。最后，我们重点介绍了如何通过结合DDR抑制剂，ICI和放射疗法来利用肿瘤细胞的自主机制。

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