肺癌是世界上发病率和死亡率最高的癌症。近年来，一种最有前途的新型癌症治疗方法是免疫疗法，其基于阻止免疫检查点（如PD-1）的作用。运动训练对维持和改善癌症患者的生活质量有益，它可能也可以调节某些化疗药物的抗肿瘤效率。然而，运动与免疫疗法结合作为肿瘤治疗的潜力仍需阐明。本研究旨在检查运动对肿瘤生长的影响，以及它与抗-PD-1免疫疗法（尼伐单抗）结合的可能辅助作用，在非小细胞肺癌（NSCLC）患者衍生异种移植模型（PDX）中进行。 我们利用NOD-SCID gamma小鼠制备了一个PDX模型，将NSCLC患者肿瘤组织的皮下移植进行。动物被随机分配到四个组中：非运动+同位素对照组（n=5），运动+同位素对照组（n=5），非运动+尼伐单抗组（n=6）或运动+尼伐单抗组（n=6）。动物进行了为期8周的中等强度训练计划（跑步机有氧运动和力量训练）。免疫疗法（尼伐单抗）或同位素对照剂量每周2次给予，共6周。干预后测量了多个肿瘤生长和微环境参数。 运动动物中注意到有氧能力和肌肉力量的改善（p= 0.027和p=0.005）。与未进行运动的小鼠相比，仅仅通过运动就减缓了肿瘤生长速度（p=0.050）。运动和尼伐单抗双重干预与对照组相比，在肿瘤坏死上增加，减少了细胞凋亡（p=0.026；p=0.030）。所有干预都在增殖方面与对照组相比有所减少（p=0.015，p=0.011和p= 0.011）。仅仅是运动就增加了肿瘤浸润（大多数是中性粒细胞），相对于仅仅使用尼伐单抗的组（p=0.018）。最后，与运动+同位素对照组相比，尼伐单抗组（结合运动和未结合运动的组）中Vegf-a表达更高（p=0.045和p=0.047）。未发现其他重要效果。 我们的结果表明，有氧和力量训练应作为癌症免疫疗法治疗的辅助研究。版权所有©2020国际运动与免疫学会。保留所有权利。

Lung cancer has the highest incidence and mortality rate in the world. One of the most promising new cancer therapies in recent years is immunotherapy, which is based on the blockade of immune checkpoints such as programmed cell death protein 1 (PD-1). Exercise training is beneficial to maintain and improve the quality of life of cancer patients, and it might also modulate the anti-tumoral efficiency of some chemotherapeutic agents. However, the potential of exercise combined with immunotherapy as a cancer therapy remains to be elucidated. Here, we examined the effects of exercise on tumor growth and its possible adjuvant effects when combined with anti-PD-1 immunotherapy (nivolumab) in a patient derived xenograft (PDX) model of non-small-cell lung carcinoma (NSCLC).We generated a PDX model using NOD-SCID gamma mice with subcutaneous grafts from tumor tissue of a patient with NSCLC. Animals were randomly assigned to one of four groups: non-exercise + isotype control (n=5), exercise + isotype control (n=5), non-exercise + nivolumab (n=6) or exercise + nivolumab (n=6). The animals undertook an 8- week moderate-intensity training regimen (treadmill aerobic exercise and strength training). Immunotherapy (nivolumab) or an isotype control was administered 2 days/week, for 6 weeks. Several tumor growth and microenvironment parameters were measured after the intervention.Improvements in aerobic capacity and muscle strength (p=0.027 and p=0.005) were noted in exercised animals. Exercise alone reduced the tumor growth rate with respect to non-exercised mice (p=0.050). The double intervention (exercise + nivolumab) increased tumor necrosis and reduced apoptosis with respect to controls (p=0.026; p=0.030). All interventions achieved a reduction in proliferation compared with the control group (p=0.015, p=0.011, and p=0.011). Exercise alone increased myeloid tumor infiltrates (mostly neutrophils) with respect to the nivolumab only group (p=0.018). Finally, Vegf-a expression was higher in the nivolumab groups (in combination or not with exercise) than in exercise + isotype control group (p=0.045 and p=0.047, respectively). No other significant effects were found.Our results would suggest that aerobic and strength training should be studied as an adjuvant to cancer immunotherapy treatment.Copyright © 2020 International Society of Exercise and Immunology. All rights reserved.