Immunotherapy has obtained a secure place in the treatment of metastatic non-small cell lung cancer (NSCLC) and has made a great impact on prognosis of responders. Unfortunately, not all NSCLC patients derive benefit from this treatment. Several immune escape mechanisms have been postulated, explaining failure of tumor immune attack. A better understanding of these mechanisms helps us to seek treatment strategies to overcome resistance to immunotherapy. Radiotherapy has immunomodulatory qualities capable of enhancing the anti-cancer immune response by tackling a number of these tumor escape mechanisms. In this review, we focus on mechanisms of off-target effects of radiotherapy, the so-called abscopal effect, by describing the current role of immune checkpoint inhibitors (ICIs) in NSCLC, the possible reasons for its failures and evidence on how radiotherapy may be able to counteract these mechanisms. An oversight of pre-clinical and clinical data supporting augmentation of abscopal events by radiotherapy when combined with ICIs is presented. As much remains unclear regarding optimal dose, fractionation, target volume or timing of radiation therapy, future research will need to focus on implementing data from pre-clinical and translational findings in the development of new clinical trials in order to help optimizing the potential of the combination of immunotherapy with radiotherapy.

中文翻译：

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通过在转移性非小细胞肺癌中结合免疫疗法和放疗来协同全身反应：潜在的潜在疗效。

免疫疗法已在转移性非小细胞肺癌（NSCLC）的治疗中获得了稳固的地位，并且对应答者的预后产生了重大影响。不幸的是，并非所有的NSCLC患者都能从这种治疗中受益。已经提出了几种免疫逃逸机制，解释了肿瘤免疫攻击的失败。对这些机制的更好理解有助于我们寻求治疗策略，以克服对免疫疗法的抵抗力。放射疗法具有免疫调节特性，能够通过解决许多这些肿瘤逃逸机制来增强抗癌免疫反应。在这篇综述中，我们通过描述免疫检查点抑制剂（ICIs）在非小细胞肺癌中的当前作用，重点研究放射疗法脱靶效应的机制，即所谓的绝对效应。其失败的可能原因，以及放疗如何能够抵消这些机制的证据。提出了对临床前和临床数据的监督，这些数据支持与ICI结合使用时通过放疗增加严重事件的发生。关于最佳剂量，分级，目标体积或放射治疗的时间尚不清楚，未来的研究将需要着重于在新的临床试验的开发中从临床前和转化结果中获取数据，以帮助优化放射治疗的潜力。免疫疗法与放射疗法的结合。