Lu Chieh-Sheng, Liu Jin-Hwang
Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung Division of Hematology/Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei Division of Hematology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
Medicine (Baltimore). 2017 Jan;96(1):e5747. doi: 10.1097/MD.0000000000005747.
In development of novel therapies for the treatment of patient with cancer, the use of radiotherapy (RT) can produce significant local control and, in recent studies, has also been shown to mediate anti-tumor responses at distant sites by triggering and enhancing the endogenous cellular immune responses. Although RT induces an abscopal effect in some patients due to enhanced immune response to the tumor, immune-escape mechanisms, including up-regulation of programmed death-ligand 1 (PD-L1) on tumor cells, limit this benefit in other patients. Hence, many studies have promoted the synergy of RT and anti-programmed cell death protein 1 (PD-1) treatment for antitumor immunity. However, outcome may be improved when more therapies are combined, but risk of side effects can be increased.
We herein present 3 advanced cancer patients with pulmonary metastasis and who received RT. Later, they underwent anti-PD-1 treatment and unfortunately suffered from anti-PD-1-related pneumonitis over the nonirradiated areas after 4 cycles of treatment. The upregulation of cellular PD-1 expression in these areas was considered and the immune overreaction by anti-PD-1 treatment may cause these severe pulmonary adverse effects.
Our review of 3 cases warrants careful workup to reduce the risk of side effects by combinative therapy with RT and anti-PD-1 treatment.
在开发用于治疗癌症患者的新疗法时,放射疗法(RT)的使用可产生显著的局部控制效果,并且在最近的研究中还显示,它可通过触发和增强内源性细胞免疫反应来介导远处部位的抗肿瘤反应。尽管RT由于增强了对肿瘤的免疫反应而在一些患者中诱导了远隔效应,但包括肿瘤细胞上程序性死亡配体1(PD-L1)上调在内的免疫逃逸机制限制了其他患者获得这种益处。因此,许多研究都促进了RT与抗程序性细胞死亡蛋白1(PD-1)治疗在抗肿瘤免疫方面的协同作用。然而,联合更多疗法可能会改善疗效,但副作用风险可能会增加。
我们在此报告3例发生肺转移并接受RT治疗的晚期癌症患者。随后,他们接受了抗PD-1治疗,不幸的是,在4个周期的治疗后,他们在未接受照射的区域出现了与抗PD-1相关的肺炎。考虑到这些区域细胞PD-1表达上调,抗PD-1治疗引起的免疫过度反应可能导致这些严重的肺部不良反应。
我们对3例病例的回顾表明,需要进行仔细的检查,以降低RT与抗PD-1联合治疗产生副作用的风险。