Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China.
Department of Internal Medicine-Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, China.
Front Immunol. 2018 Dec 11;9:2916. doi: 10.3389/fimmu.2018.02916. eCollection 2018.
Preclinical and clinical studies have shown that prior receipt of radiotherapy enhances antitumor immune responses, a phenomenon we call the "radio-memory effect." However, all of the evidence regarding this effect to date comes from work with PD1/PDL1 inhibitors. Here we explored whether this effect also occurs with other forms of immune therapy, specifically interleukin-2 (IL-2). We retrospectively assessed outcomes in patients with malignant pleural effusion (MPE) who had previously received radiotherapy for non-small-cell lung cancer (NSCLC) within 18 months before the intrapleural infusion of IL-2 or cisplatin. Radiotherapy sites included lungs, thoracic lymph nodes, and intracranial. All patients received intrapleural infusion of IL-2 or cisplatin, and most had had several cycles of standard chemotherapy for NSCLC. We identified 3,747 patients with MPE (median age 64 years [range 29-88)) treated at one of several institutions from August 2009 through February 2015; 642 patients had been treated with IL-2 and 1102 with cisplatin and had survived for at least 6 months afterward. Among those who received IL-2, 288 had no radiotherapy, 324 had extracranial (i.e., thoracic) radiotherapy, and 36 had intracranial radiotherapy. The median follow-up time for surviving patients was 38 months. Patients who had received extracranial radiotherapy followed by IL-2 had significantly longer PFS than patients who had not received extracranial radiotherapy (i.e., either no radiotherapy or intracranial radiotherapy). Patients who had received intracranial or extracranial radiotherapy followed by IL-2 had significantly longer OS than did other patients. No survival advantage was noted for prior radiotherapy among patients who received intrapleural cisplatin. We speculate that previous radiotherapy could enhance the efficacy of subsequent intrapleural infusion of IL-2, a "radio-memory" effect that could be beneficial in future studies.
临床前和临床研究表明，先前接受放疗可增强抗肿瘤免疫反应，这种现象我们称之为“放疗记忆效应”。然而，迄今为止，所有关于这种效应的证据都来自于 PD1/PDL1 抑制剂的研究。在这里，我们探讨了这种效应是否也会发生在其他形式的免疫治疗中，特别是白细胞介素-2（IL-2）。我们回顾性评估了先前在胸腔内输注 IL-2 或顺铂前 18 个月内接受非小细胞肺癌（NSCLC）放疗的恶性胸腔积液（MPE）患者的结局。放疗部位包括肺部、胸内淋巴结和颅内。所有患者均接受胸腔内输注 IL-2 或顺铂治疗，大多数患者曾接受过多次 NSCLC 标准化疗。我们从 2009 年 8 月至 2015 年 2 月在几家机构治疗的 3747 例 MPE 患者中识别出（中位年龄 64 岁[范围 29-88 岁]）；642 例接受 IL-2 治疗，1102 例接受顺铂治疗，且至少在治疗后 6 个月存活。在接受 IL-2 治疗的患者中，288 例未接受放疗，324 例接受了颅外（即胸外）放疗，36 例接受了颅内放疗。生存患者的中位随访时间为 38 个月。与未接受颅外放疗的患者相比，接受颅外放疗后再接受 IL-2 治疗的患者 PFS 显著延长（即未接受放疗或颅内放疗）。接受颅内或颅外放疗后再接受 IL-2 治疗的患者 OS 显著长于其他患者。接受胸腔内顺铂治疗的患者中，先前放疗无生存优势。我们推测，先前的放疗可以增强随后胸腔内输注 IL-2 的疗效，这种“放疗记忆”效应可能对未来的研究有益。
