Parent-Roberge Hugo, Fontvieille Adeline, Poirier Laurence, Tai Lee-Hwa, Pavic Michel, Fülöp Tamàs, Riesco Eléonor
University of Sherbrooke, Faculty of Physical Activity Sciences, 2500, boul. de l'Université, Sherbrooke, Qc, J1K 2R1, Canada.
Research Centre on Aging, affiliated with CIUSSS de l'Estrie - CHUS, 1036, rue Belvédère sud, Sherbrooke, Qc, J1H 4C4, Canada.
Brain Behav Immun Health. 2024 Jul 17;40:100825. doi: 10.1016/j.bbih.2024.100825. eCollection 2024 Oct.
It has been suggested that the acute natural killer (NK) cell response to aerobic exercise might contribute to the tumor suppressor effect of regular exercise observed in preclinical studies. Moreover, because this response is modulated by exercise intensity, high-intensity intervals exercise (HIIE) might represent an interesting therapeutic approach in cancer patients. However, this immune response remains unstudied in cancer patients currently undergoing chemotherapy.
To characterize the acute NK cell response following a moderate-intensity continuous aerobic exercise session (MOD), and a HIIE session in metastatic cancer patients treated with chemotherapy.
Twelve cancer patients (45-65 years old) underwent a MOD and a duration and work-matched HIIE trial, in a block-randomized order. Peripheral blood mononuclear cells (PBMC) were isolated before, after and 1h after each trial. NK cell subsets were enumerated using flow cytometry and complete blood counts. The surface expression of the cytotoxic NK cell (cNK; CD56CD16) subset was evaluated for its expression of the differentiation markers CD57 and CD158a, the activating receptor NKG2D, the immune checkpoints TIM-3 and PD-1, and the chemokine receptors CXCR3, CXCR4 and CCR2.
cNK cell blood counts increased immediately following MOD (p < 0.001) and decreased back to pre-exercise values 1 h after exercise cessation (p < 0.001). The most responsive cNK cell subsets were expressing CD57, CD158a, NKG2D, TIM-3 and CXCR3. The HIIE trial elicited a similar biphasic response, without any difference between trials (all p ≥ 0.38). However, significant changes in the MFI values of CXCR4 and NKG2D were observed in the cNK cell subset following HIIE (all p ≤ 0.038), but not MOD.
In metastatic cancer patients undergoing chemotherapy, both MOD and HIIE can elicit an acute mobilisation and egress of NK cells exhibiting phenotypic characteristics associated with high cytotoxicity and tumor homing. Future longitudinal trials are needed to determine if combining aerobic exercise training and chemotherapy will translate towards favorable immune and clinical outcomes.
有研究表明，有氧运动引起的急性自然杀伤（NK）细胞反应可能有助于解释临床前研究中观察到的规律运动的肿瘤抑制作用。此外，由于这种反应受运动强度调节，高强度间歇运动（HIIE）可能是一种针对癌症患者的有趣治疗方法。然而，目前正在接受化疗的癌症患者的这种免疫反应仍未得到研究。
描述转移性癌症化疗患者在进行中等强度持续有氧运动（MOD）和HIIE训练后的急性NK细胞反应特征。
12名癌症患者（45 - 65岁）以区组随机顺序进行了MOD和时长及工作量匹配的HIIE试验。在每次试验前、试验后及试验后1小时分离外周血单个核细胞（PBMC）。使用流式细胞术和全血细胞计数对NK细胞亚群进行计数。评估细胞毒性NK细胞（cNK；CD56CD16）亚群的表面表达，检测其分化标志物CD57和CD158a、活化受体NKG2D、免疫检查点TIM - 3和PD - 1以及趋化因子受体CXCR3、CXCR4和CCR2的表达情况。
MOD后cNK细胞计数立即增加（p < 0.001），运动停止1小时后降至运动前水平（p < 0.001）。反应最明显的cNK细胞亚群表达CD57、CD158a、NKG2D、TIM - 3和CXCR3。HIIE试验引发了类似的双相反应，各试验之间无差异（所有p≥0.38）。然而，HIIE后cNK细胞亚群中CXCR4和NKG2D的平均荧光强度（MFI）值有显著变化（所有p≤0.038），而MOD后未观察到这种变化。
在接受化疗的转移性癌症患者中，MOD和HIIE均可引发NK细胞的急性动员和流出，这些NK细胞表现出与高细胞毒性和肿瘤归巢相关的表型特征。未来需要进行纵向试验，以确定有氧运动训练与化疗相结合是否会带来良好的免疫和临床结果。
