Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Epidemiology and Biostatistics, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Public Health, Amsterdam, The Netherlands.
Physiol Rep. 2021 Jun;9(11):e14919. doi: 10.14814/phy2.14919.
Natural killer (NK) cells are a population of innate immune cells known to play a pivotal role against tumor spread. In multiple murine models, it was shown that physical exercise had the potential to increase NK cell antitumor activity through their mobilization and tissue redistribution in an interleukin (IL)-6 and epinephrine-dependent manner. The translation of this finding to patients is unclear. In this randomized pilot trial, we analyzed blood samples of patients with resectable breast or colon cancer who were randomized into an evidence-based moderate-high intensity resistance and aerobic exercise intervention (n = 8) or a control group (n = 6) during the first 9-12 weeks of (neo)adjuvant chemotherapy. In this pilot, we did not solely focus on statistical significance, but also explored whether average between-group differences reached 10%. NK cell degranulation was preserved in the exercise group whereas it decreased in the control group resulting in a between-group difference of 11.4% CD107a degranulated NK cells (95%CI = 0.57;22.3, p = 0.04) in the presence and 13.8% (95%CI = -2.5;30.0, p = 0.09) in the absence of an anti-epidermal growth factor receptor monoclonal antibody (EGFR-mAb). In line, the between-group difference of tumor cell lysis was 7.4% (95%CI = -9.1;23.9, p = 0.34), and 13.7% (95%CI = -10.1;37.5, p = 0.23) in favor of the exercise group in the presence or absence of EGFR mAb, respectively. Current explorative analyses showed that exercise during (neo)adjuvant chemotherapy may benefit NK cell activity. Future studies with a larger sample size are needed to confirm this finding and to establish its clinical potential. Trial registration: Dutch trial register number NTR4105.
自然杀伤 (NK) 细胞是先天免疫细胞的一个群体，已知其在对抗肿瘤扩散方面发挥着关键作用。在多个小鼠模型中，运动通过白细胞介素 (IL)-6 和肾上腺素的依赖性，使 NK 细胞的动员和组织再分布，具有增加 NK 细胞抗肿瘤活性的潜力。这一发现转化为患者尚不清楚。在这项随机试点试验中，我们分析了可切除乳腺癌或结肠癌患者的血液样本，这些患者在 (新)辅助化疗的前 9-12 周被随机分为循证中高强度抵抗和有氧运动干预组（n=8）或对照组（n=6）。在这个试点中，我们不仅关注统计学意义，还探索了平均组间差异是否达到 10%。运动组 NK 细胞脱颗粒保持不变，而对照组 NK 细胞脱颗粒减少，导致存在抗表皮生长因子受体单克隆抗体 (EGFR-mAb) 时，CD107a 脱颗粒 NK 细胞的组间差异为 11.4%（95%CI=0.57；22.3，p=0.04），不存在 EGFR-mAb 时，组间差异为 13.8%（95%CI=-2.5；30.0，p=0.09）。相应地，在存在或不存在 EGFR-mAb 时，肿瘤细胞裂解的组间差异分别为 7.4%（95%CI=-9.1；23.9，p=0.34）和 13.7%（95%CI=-10.1；37.5，p=0.23），有利于运动组。目前的探索性分析表明，在 (新)辅助化疗期间进行运动可能有益于 NK 细胞活性。需要更大样本量的未来研究来证实这一发现，并确定其临床潜力。试验注册：荷兰试验注册编号 NTR4105。
