Table_1_A novel [89Zr]-anti-PD-1-PET-CT to assess response to PD-1/PD-L1 blockade in lung cancer.docx

BackgroundHarnessing the anti-tumor immune system response by targeting the program cell death protein (PD-1) and program cell death ligand protein (PD-L1) axis has been a major breakthrough in non-small cell lung cancer (NSCLC) therapy. Nonetheless, conventional imaging tools cannot accurately assess response in immunotherapy-treated patients. Using a lung cancer syngeneic mouse model responder to immunotherapy, we aimed to demonstrate that [89Zr]-anti-PD-1 immuno-PET is a safe and feasible imaging modality to assess the response to PD-1/PD-L1 blockade in NSCLC.Materials and methodsA syngeneic mouse model responder to anti-PD-1 therapy was used. Tumor growth and response to PD-1 blockade were monitored by conventional 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) PET scans. Additionally, tumor lymphocyte infiltration was analyzed by the use of an [89Zr]-labeled anti-PD-1 antibody and measured as 89Zr tumor uptake.ResultsConventional [18F]-FDG-PET scans failed to detect the antitumor activity exerted by anti-PD-1 therapy. However, [89Zr]-anti-PD-1 uptake was substantially higher in mice that responded to PD-1 blockade. The analysis of tumor-infiltrating immune cell populations and interleukins demonstrated an increased anti-tumor effect elicited by activation of effector immune cells in PD-1-responder mice. Interestingly, a positive correlation between [89Zr]-anti-PD-1 uptake and the proportion of tumor-infiltrating lymphocytes (TILs) was found (Cor = 0.8; p = 0.001).ConclusionOur data may support the clinical implementation of immuno-PET as a promising novel imaging tool to predict and assess the response of PD-1/PD-L1 inhibitors in patients with NSCLC.

背景：针对程序性细胞死亡蛋白（PD-1）及其配体蛋白（PD-L1）轴的免疫反应抑制已成为非小细胞肺癌（NSCLC）治疗领域的一项重大突破。然而，传统的成像工具难以准确评估免疫治疗患者的治疗效果。本研究采用对免疫治疗有响应的肺癌同基因小鼠模型，旨在证明[89Zr]-抗PD-1免疫-PET是一种安全且可行的成像方法，用以评估NSCLC中PD-1/PD-L1阻断剂的治疗反应。材料与方法：采用对抗PD-1疗法有响应的同基因小鼠模型。通过常规的2-脱氧-2-[18F]氟代-D-葡萄糖（[18F]-FDG）PET扫描监测肿瘤生长及对PD-1阻断剂的反应。此外，利用[89Zr]标记的抗PD-1抗体分析肿瘤淋巴细胞浸润，并测量89Zr肿瘤摄取。结果：常规的[18F]-FDG-PET扫描未能检测到抗PD-1疗法所发挥的抗肿瘤活性。然而，对PD-1阻断剂有响应的小鼠中[89Zr]-抗PD-1的摄取显著增加。对肿瘤浸润性免疫细胞群体和细胞因子的分析显示，在PD-1响应小鼠中，效应性免疫细胞的激活产生了增强的抗肿瘤效果。有趣的是，[89Zr]-抗PD-1摄取与肿瘤浸润淋巴细胞（TILs）的比例呈正相关（相关系数 = 0.8；p = 0.001）。结论：本研究数据可能支持免疫-PET作为一项有前景的新型成像工具，在预测和评估NSCLC患者中PD-1/PD-L1抑制剂的治疗反应方面的临床应用。