The Centre for Physical Activity Research (CFAS) and Centre of Inflammation and Metabolism (CIM), Copenhagen University Hospital, 7641, University of Copenhagen, Copenhagen, Denmark.
Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
Acta Oncol. 2020 Dec;59(12):1447-1454. doi: 10.1080/0284186X.2020.1817550. Epub 2020 Sep 16.
Exercise and physical activity (PA) are associated with reduced tumor growth and enhanced intra-tumoral immune cell infiltration in mice. We aimed to investigate the role of PA achieved by voluntary wheel running in promoting the immunogenic profile across several murine tumor models, and to explore the potential of checkpoint blockade and PA in the form of voluntary wheel running as combination therapy.
The experiments were performed with C57BL/6 mice bearing subcutaneous tumors while having access to running wheels in their cages, where key immunoregulatory molecules expressed in the tumor tissue were measured by qPCR. Furthermore, we tested the hypothesis that wheel running combined with PD-L1 -or PD-1 inhibitor treatment could lead to an additive effect on tumor growth in mice bearing B16 melanoma tumors.
Wheel running increased immune checkpoint expression (PD-1, PD-L1, PD-L2, CD28, B7.1 and B7.2) in B16 tumor-bearing mice, while induction of only PD-L2 was found in E0771 breast cancer and Lewis Lung Cancer. In studies combining voluntary wheel running with PD-1 -and PD-L1 inhibitors we found significant effects of wheel running on attenuating B16 melanoma tumor growth, in line with previous studies. We did, however, not find an additive effect of combining either of the two immunotherapeutic treatments with access to running wheels.
B16 tumors displayed upregulated expression of immune regulatory molecules and decreased tumor growth in response to PA. However, combining PA with PD-1 or PD-L1 blockade did not lead to a further augmented inhibition of tumor growth.
运动和身体活动（PA）与减少肿瘤生长和增强肿瘤内免疫细胞浸润有关。我们旨在研究通过自愿轮跑实现的 PA 在促进几种小鼠肿瘤模型的免疫原性特征方面的作用，并探索检查点阻断和自愿轮跑形式的 PA 作为联合治疗的潜力。
实验在皮下肿瘤的 C57BL/6 小鼠中进行，同时在笼子里提供跑步轮，通过 qPCR 测量肿瘤组织中表达的关键免疫调节分子。此外，我们测试了轮跑与 PD-L1 或 PD-1 抑制剂联合治疗可能导致对携带 B16 黑色素瘤肿瘤的小鼠肿瘤生长产生附加效应的假设。
轮跑增加了 B16 荷瘤小鼠的免疫检查点表达（PD-1、PD-L1、PD-L2、CD28、B7.1 和 B7.2），而在 E0771 乳腺癌和 Lewis 肺癌中仅诱导了 PD-L2 的表达。在结合自愿轮跑与 PD-1 和 PD-L1 抑制剂的研究中，我们发现轮跑对减轻 B16 黑色素瘤肿瘤生长有显著影响，与以前的研究一致。然而，我们没有发现将两种免疫治疗方法中的任何一种与轮跑相结合会产生附加效果。
B16 肿瘤显示出免疫调节分子的上调表达和对 PA 的肿瘤生长减少。然而，将 PA 与 PD-1 或 PD-L1 阻断结合并没有导致肿瘤生长的进一步增强抑制。
