Table 1 Main characteristics of the included studies
Study | Cancer and treatment | Study groups | Exercise training intervention | Technique | Variable | Results (main exercise training effects) |
|---|---|---|---|---|---|---|
Fairey et al. [29] | Stage I to IIIB breast cancer | Exercise: N = 25 (24 analyzed) 59 ± 5 years | Modality: supervised aerobic training | Flow cytometry | Percentage of NK cells in PBMCs | ↔ NK cells |
Completed surgery, radiotherapy and/or chemotherapy (14 ± 6 months prior to enrollment) with/without tamoxifen or anastrozole therapy | Length and frequency: 15 weeks, 3 days/week | 51Cr release assay K562 as the target cell | NKCA in PBMCs: percentage of 51Cr release and PBMCs corrected to a per cell basis (lytic units/103, number of effector cells required to cause 30% lysis of target cells) | ↑ NKCA at all E:T ratios | ||
Control: N = 28; 58 ± 6 years | Duration: 15 – 35 min | E:T ratios = 50:1, 25:1, 12.5:1, 6.25:1, 3.125:1 | ||||
Intensity: ~70–75% VO2peak | ||||||
Fiuza-Luces et al. [33] | Extracranial solid tumors | Exercise: N = 25 (9 analyzed) 11.0 ± 4.0 years | Modality: supervised aerobic and resistance training | Flow cytometry | Absolute number and percentage of NK cells, NK cell subsets (NKbright and NKdim) and NK cells expressing different activating or inhibitory receptors in total blood | ↔ NK cell |
During neoadjuvant chemotherapy | Control: N = 24 (11 analyzed) 12.0 ± 4.0 years | Length and frequency: the neoadjuvant chemotherapy period (19 ± 2 weeks), 3 days/week in gym sessions or 5 days/week in ward sessions | ↔ NK cell receptors | |||
Europium-TDA release assay | NKCA in PBMCs: percentage of K562 lysis | ↔ NKCA | ||||
Duration: 30 min of aerobic training; 30 min of resistance training | K562 as the target cell | |||||
E:T ratios = 8:1. 4:1, 2:1, 1:1 | ||||||
Intensity: 60–70% HRmax (aerobic training); intensity progressively increased (resistance training) | ||||||
Glass et al. [44] | Solid tumors (mainly breast cancer) | Exercise: N = 26 (23 analyzed) 56 ± 10 years | Modality: supervised aerobic training | Flow cytometry | Percentage of NK cells in PBMCs | ↔ NK cells |
During cytotoxic therapy and synthetic erythropoietin therapy | Length and frequency: 12 weeks, 3 days/week | |||||
Control: N = 29 (21 analyzed) 54 ± 11 years | Duration: 20–45 min | |||||
Intensity: 55–100% VO2peak | ||||||
Hagstrom et al. [28] | Stage I to IIIA breast cancer | Exercise: N = 20 (19 analyzed) 51.2 ± 8.5 years | Modality: supervised resistance training | Flow cytometry | Percentage of NK cells in total blood | ↔ NK cells |
Completed surgery, radiotherapy and/or chemotherapy (11.5 months average prior to enrollment) with/without hormone therapy | Length and frequency: 16 weeks, 3 days/week | Flow cytometry | Percentage of functional markers (granzyme B and perforin) of NKCA in total blood | ↔ granzyme B and perforin expression in NK cells | ||
Control: N = 19 (15 analyzed) 52.7 ± 9.4 years | Duration: 60 min | Flow cytometry | Percentage of NK cell intracellular cytokine (TNFɑ and IFNγ) production in total blood | ↓ NK cell expression of TNFɑ | ||
Intensity: 8-RM | ||||||
Kaushik et al. [42] | Prostate cancer | Exercise N = 14 (12 analyzed) 56 (55–61) years | Modality: supervised Hatha yoga | Flow cytometry | Frequency and absolute number of NK cells and CD56bright and CD56dim NK cells in preactivated PBMCs | ↔ NK cells |
Perioperative (radical prostatectomy) period | Control N = 15 (14 analyzed) 60 (59–61) Years | Length and frequency: 6 weeks preoperatively + 6 weeks starting 3–6 weeks postoperatively, 2 days/week | Flow cytometry | Cytokine response in NK cells from preactivated PBMCs | ↑ Fc receptor III production and IFN-γ expression in NK cells | |
Duration: 60 min | ||||||
Intensity: adapted to patients’ comfort level | ||||||
Ligibel et al. [35] | Breast cancer | Exercise: N = 27 (14 analyzed) 52.3 ± 9.6 years | Modality: supervised and unsupervised aerobic/resistance training | Immunohistochemistry | Percentage of NK cells in tumor tissue | ↔ NK cells |
Preoperative breast surgery | Length and frequency: mean of 29.3 days, 2 days/week | |||||
Control: N = 22 (11 analyzed) 53.1 ± 7.9 years | Duration: 180 min of aerobic training and 40 min of resistance training | |||||
Intensity: moderate | ||||||
Liu et al. [41] | Stages I to IIIB non-small cell lung cancer | Exercise: N = 16 (14 analyzed) 62.6 ± 8.4 years | Modality: supervised Tai Chi | Flow cytometry | Percentage of NK cells in total blood | ↑ NK cells |
Post-surgery (≥ 2 years prior to enrollment) | Length and frequency: 16 weeks, 3 days/week | Cell viability assay | NKCA in PBMCs: tumor cell viability assay | ↑ NKCA at 25:1 and 50:1 E:T ratios | ||
Control: N = 16 (13 analyzed) 60.5 ± 7.1 years | Duration: 60 min | A549 as the target cell | ||||
Intensity: moderate | E:T cell ratios = 50:1, 25:1, 12.5:1 | |||||
Mohamady et al. [36] | Breast cancer | Exercise: N = 20, 40–60 years | Modality: supervised and home-based training. Proprioceptive neuromuscular facilitation, resistance training and aerobic training | Flow cytometry | Number of NK cells in total blood | ↑ NK cells |
Post-surgery | Control: N = 20, 40–60 years | Length and frequency: 12 weeks, twice a day, 3 – 7 days/week | ||||
Duration: 30 min | ||||||
Intensity: moderate | ||||||
Na et al. [30] | Stomach cancer | Exercise: N = 17, 57.8 ± 12.1 years | Modality: supervised mobility exercises and resistance training (in bed) and supervised aerobic training (ambulatory setting) | 51Cr release assay | NKCA in PBMCs: percentage of specific 51Cr release | ↑ NKCA |
Post-surgery | Control: N = 18, 52.2 ± 10.3 years | Length and frequency: 2 weeks. Exercise in bed: 3 times a day. Ambulatory setting: 5 days/week, twice a day | K562 as the target cell | |||
Duration: 30 min | E:T ratio = 50:1 | |||||
Intensity: 60% HRmax (aerobic training); isometric (resistance training) | ||||||
Nieman et al. [32] | Breast cancer | Exercise: N = 8 (6 analyzed) 60.8 ± 4.0 years | Modality: supervised aerobic and resistance training | Flow cytometry | Percentage of NK cells in total blood | ↔ NK cells |
Completed surgery, chemotherapy and/or radiotherapy within the previous 3.0 ± 1.2 years | Length and frequency: 8 weeks, 3 days/week | 51Cr release assay | NKCA in PBMCs: percentage of 51Cr release | ↔ NKCA | ||
Control: N = 8 (6 analyzed) 51.2 ± 4.7 years | Duration: 30 min of aerobic training and 30 min of resistance training | K562 as the target cell | ||||
Intensity: 75% HRmax (aerobic training); intensity progressively increased (resistance training) | E:T ratios = 40:1, 20:1 | |||||
Sagarra-Romero et al. [37] | Stage I and II breast cancer | Exercise: N = 11 (10 analyzed) 50.0 ± 5.5 years | Modality: supervised aerobic and resistance training | N/R | Percentage of NK cells in total blood | ↔ NK cells |
Undergone surgery and receiving adjuvant chemotherapy | Length and frequency: 18–22 weeks, 3 days/week | |||||
Control: N = 11 (7 analyzed) 53.1 ± 6.8 years | Duration: 45 min; 20 min of aerobic training and 25 min of resistance training | |||||
Intensity: 60–70% VO2peak (aerobic training) and N/R for resistance training | ||||||
Schmidt et al. [45] | Primary moderate- or high-risk breast cancer | Strength exercise: N = 21, 53 ± 12.6 years | Modality: supervised aerobic or resistance training | Flow cytometry | Absolute number of NK cells in total blood | ↔ NK cells |
From the initiation of chemotherapy to the end of epirubicin or cyclophosphamide therapy | Aerobic exercise: N = 20, 56 ± 10.2 years | Length and frequency: 12 weeks, twice weekly | ||||
Duration: 60 min | ||||||
Control: N = 26, 54 ± 11.2 years | Intensity: Borg scale of 11–14 (aerobic training) and 50% of the maximum weight with increments based on Borg scale (resistance training) | |||||
Toffoli et al. [43] | Resectable colon (stage II/III) or breast cancer (stage I/II/III) | Exercise: N = 8 (4 for the expression of NK cell receptors) 55.1 ± 14.8 years | Modality: supervised aerobic and resistance training | Flow cytometry | NK cell subsets (NKbright and NKdim) and NK cells expressing different activating or inhibitory receptors in total blood | ↑ NKp46 (activating receptor) on CD56dim CD16+ NK cells |
During neoadjuvant chemotherapy | Control: N = 6 (4 for the expression of NK cell receptors) 60.7 ± 7.6 years | Length and frequency: during the first 9–12 weeks or treatment, twice weekly | NK cell degranulation and cytotoxicity assay by flow cytometry | NK cell degranulation in monocyte-depleted PBMCs: percentage of CD107a+ NK cells | ↔ NK cell degranulation | |
Duration: 60 min | A431 as the target cell | |||||
Intensity: moderate to high | E:T ratio = 4:1 | NKCA in monocyte-depleted PBMCs: relative percentage of cytotoxicity (of living tumor cells) | ↔ NKCA |