Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, China.
Department of Surgery, Department of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
BMC Med. 2020 Sep 18;18(1):275. doi: 10.1186/s12916-020-01718-3.
The synergistic effect of radiotherapy (RT) in combination with immunotherapy has been shown in several clinical trials and case reports. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. Thus far, the underlying mechanism of this toxicity remains largely unknown.
In this review, we discuss the unique pattern of radiation recall pneumonitis (RRP) induced by PD-1 blockade. The clinical presentation is different from common radiation pneumonitis (RP) or RRP induced by cytotoxic drugs. The immune checkpoint inhibitors may evoke an inflammatory reaction in patients' previously irradiated fields, with infiltrating lymphocytes and potential involvement of related cytokines. All RRP patients have showed durable response to anti-PD-1/PD-L1. RRP is manageable; however, interruption of checkpoint blockades is necessary and immunosuppressive treatment should be started immediately. Further analyses of the predictive factors, including RT dosimetric parameters, tumor-infiltrating lymphocytes (TILs), and PD-L1 expression, are needed given the wide use of immune checkpoint inhibitors and high mortality from lung toxicity with the combination treatment.
Immune checkpoint inhibitors may evoke an RRP in the patients' previously irradiated fields. Interactions between immune checkpoint inhibitors and radiotherapy should be studied further.
放射治疗（RT）与免疫疗法联合的协同效应已在几项临床试验和病例报告中得到证实。胸部 RT 和程序性死亡 1/程序性死亡配体 1（PD-1/PD-L1）阻断联合治疗中，由放射性肺炎重叠引起的肺毒性是临床研究的一个重要问题。到目前为止，这种毒性的潜在机制在很大程度上仍不清楚。
在这篇综述中，我们讨论了 PD-1 阻断引起的独特放射性回忆性肺炎（RRP）模式。临床表现与常见的放射性肺炎（RP）或细胞毒性药物引起的 RRP 不同。免疫检查点抑制剂可能会在患者先前照射的区域引发炎症反应，伴有浸润淋巴细胞和潜在相关细胞因子的参与。所有 RRP 患者均对 PD-1/PD-L1 表现出持久的反应。RRP 是可以控制的；然而，需要中断检查点阻断，并立即开始免疫抑制治疗。鉴于免疫检查点抑制剂的广泛应用以及联合治疗导致的高死亡率，需要对预测因素（包括 RT 剂量学参数、肿瘤浸润淋巴细胞（TILs）和 PD-L1 表达）进行进一步分析。
免疫检查点抑制剂可能会在患者先前照射的区域引发 RRP。应进一步研究免疫检查点抑制剂和放射治疗之间的相互作用。
