Effect of Exercise on Immune System Markers in Cancer Patients and Survivors: A Systematic Review

Table 4. Results of the included studies with participants in active treatment.

First Author, Year	Cancer	Intervention	Sample size (age, years)	Treatment	Collection Methods and Endpoints	Outcomes
First Author, Year	Cancer	Intervention	Sample size (age, years)	Treatment	Collection Methods and Endpoints	Within-groups	Between-groups
Schmidt et al. (2018)	Breast cancer	12-week G1: 60 min, 2x/wk; 1 set of 20 reps with a hypothetical 50% of the maximum weight G2: 60 min, 2x/wk; indoor bike, 10 min warm-up, 25-30 min, and 5 min cool-down; level 11-14 on Borg scale G3: Usual care	N: 67 G1: 21 (53y) G2: 20 (56y) G3: 26 (54y)	Adjuvant CTx	Time points: Baseline 12 weeks End of the intervention Collection methods Flow cytometry BD Multitest 6-color TBNK (M6T) Reagent with BD Trucount Beads	CD3+ T: G1 - Pre: 1252.82 ± 422.86; Post: 1010.81 ± 484.96; p = 0.46 G2 - Pre: 1153.40 ± 365.05; Post: 856.00 ± 379.00; p = 0.001 G3 - Pre: 1255.48 ± 340.32; Post: 985.00 ± 323.98; p = 0.001 TCR αβ: G1 - Pre: 1209.76 ± 411.78; Post: 969.38 ± 473.59; p = 0.04 G2 - Pre: 1112.35 ± 355.27; Post: 820.70 ± 358.57; p = 0.00 G3 - Pre: 1203.64 ± 328.85; Post: 940.48 ± 308.83; p = 0.00 TCR γδ: G1 - Pre: 42.67 ± 25.96; Post: 43.05 ± 29.74; p = 0.95 G2 - Pre: 41.75 ± 47.66; Post: 35.00 ± 52.45; p = 0.14 G3 - Pre: 53.84 ± 66.48; Post: 45.80 ± 48.65; p = 0.12 CD8+ T: G1 - Pre: 359.67 ± 156.92; Post: 320.33 ± 208.24; p = 0.13 G2 - Pre: 339.40 ± 173.98; Post: 282.05 ± 152.28; p = 0.04 G3 - Pre: 369.84 ± 150.37; Post: 355.00 ± 170.71; p = 0.41 CD4+ T: G1 - Pre: 827.33 ± 317.86; Post: 562.86 ± 210.31; p = 0.001 G2 - Pre: 753.60 ± 259.90; Post: 488.75 ± 192.85; p = 0.001 G3 - Pre: 788.60 ± 199.43; Post: 558.60 ± 159.44; p = 0.001 NK: G1 - Pre: 230.14 ± 118.26; Post: 177.48 ± 118.05; p = 0.53 G2 - Pre: 182.65 ± 82.44; Post: 109.30 ± 42.30; p = 0.001 G3 - Pre: 188.76 ± 79.30; Post: 152.16 ± 99.20; p = 0.05 B cells: G1 - Pre: 191.81 ± 78.78; Post: 25.71 ± 33.09; p = 0.001 G2 - Pre: 172.70 ± 71.93; Post: 12.80 ± 11.07; p = 0.001 G3 - Pre: 183.20 ± 79.71; Post: 20.6 ± 20.08; p = 0.001	Not significant
Li et al. (2024)	Stage II–IV lung cancer patients	12 weeks G1: exercise health education and exercise guidance (30 min daily brisk walking at RPE 13, 5 day/wk, and two resistance training sessions per week, each lasting 20 min G2: general health education materials	N: 38 G1: 21 (14 ≤ 65y; 7 > 65y) G2: 17 (8 ≤ 65y; 9 > 65y)	Adjuvant CTx	Time points: Baseline Mid-intervention End of intervention	Eosinophil percentage (p = 0.668): Ø, Neutrophil to-lymphocyte ratio (NLR) (p = 0.543): Ø; Platelet-to-lymphocyte ratio (PLR) (p = 0.430): Ø	Eosinophil percentage (p = 0.985): Ø NLR (p = 0.167): Ø PLR (p =0.668): Ø
Mijwel et al. (2020)	Breast cancer	16 weeks G1: 2x/wk, 60 minutes; 2-3 sets of 8–12 reps at @70-80% 1-RM; HIIT: 3x 3 min/1 min bouts at RPE 16 to 18 on a cycle ergometer. G2: 2x/wk, 60 minutes; 20 min of MICT, 13-15 RPE; same HIIT as in G1 G3: Usual care	N: 206 G1: 74 (52.7y) G2: 72 (54.4y) G3: 60 (52.6y)	Adjuvant CTx	Time points: Baseline End of intervention Collection methods: Not described.	Not reported	Thrombocyte concentration G1 > G3 (prior to 3rd CTx session) - 95% CI, 0.84 to 54.47 × 109/L; p = .04) G1 > G3 (prior to the 5th session) - 95% CI, 3.78 to 57.62 × 109/L; p = .019 G1 > G2 (prior to the 5th session) - 95% CI, 0.09 to 52.95 × 109/L; p = .05) Concentrations of: Hemoglobin: Ø Lymphocyte: Ø Neutrophil: Ø Incidence of thrombocytopenia G1 < G3 – G1 vs. G3: OR, 0.27; p = 0.03; G2 < G3 - G2 vs. G3: OR, 0.24; p = 0.01)
Chuang et al., (2017)	Non-Hodgkin Lymphoma	21-day, 2-3x/day G1: Chan-Chuang qigong intervention; 5min warm up, 15min main course and a 5min cool-down. G2: Usual Care	N: 96 G1: 48 (55.85y) G2: 48 (64.54y)	CTx	Time points: Baseline End of intervention Collection methods: Beckman automatic blood analyser	Not reported	White blood cell counts: G1 - Pre: 4731.46 ± 2074.34; Post: 6478.33 ± 4222.05 G2 - Pre: 5482.29 ± 3460.63; Post: 4150.42 ± 2142.67 G1 vs G2 - t = 5.14, p < 0.001 Platelet counts: Ø
Zimmer et al. (2014)	Non-Hodgkin Lymphoma	30 min G1 and G3: 30 min on a bicycle ergometer at moderate intensity (13–14 RPE) immediately after t1. G2 and G4: Usual care	N: 36 (26 patients and 10 healthy controls) G1: 14 G2: 12 G3: 5 G4: 5 G1 and G2 (62.2y) G3 and G4 (56.6y)	CTx	Time points: Baseline Baseline plus 1h Collection methods: Ficoll-based density-gradient centrifugation protocol Magnetic-activated cell sorting.	ΔCD8H4K5: G1: ↑ (p = 0.041)	Not reported
Fiuza-Luces et al. (2017)	Synovial sarcoma Ewing sarcoma Osteosarcoma Burkitt lymphoma Neuroblastoma Hodgkin lymphoma Diffuse large B-cell lymphoma T-cell lymphoblastic lymphoma Ganglioneuroblastoma	The mean duration of the exercise intervention: 17(5) wks G1: 3x/wk; 60- to 70-min; inhospital; Aerobic training: 30 mins (60 to 70% max HR); resistance training: 30 mins (2 to 3 sets of 8-15 reps) G2: Physiotherapy	N: 20 G1: 9 (11y) G2: 11 (12y)	Neoadjuvant CTx	Time points: Baseline End of the treatment 2 months after the end of the treatment Collection methods: Multiparametric flow cytometry Polymerase chain reaction	Leukocytes - G1 - Pre: 8.6 ± 1.3; Post: 5.8 ± 1.9; Detraining: 6.0 ± 3.5; G2 - Pre: 8.5 ± 1.6; Post: 6.2 ± 1.8; Detraining: 4.7 ± 1.2; p = 0.756 T cells (%) G1 - Pre: 67.4 ± 4.1; Post: 55.2 ± 5.5; Detraining: 53.4 ± 5.7; G2 - Pre: 50.5 ± 6.3; Post: 56.2 ± 7.7; Detraining: 57.2 ± 4.0; p = 0.933 B cells (%): G1 - Pre: 14.8 ± 2.9; Post: 8.1 ± 3.9; Detraining: 13.1 ± 4.5; G2 - Pre: 13.1 ± 2.4; Post: 3.5 ± 1.0; Detraining: 4.1 ± 1.5; p = 0.013 NK cells (%): G1 - Pre: 7.1 ± 2.0; Post: 16.9 ± 2.6; Detraining: 16.4 ± 3.5; G2 - Pre: 11.3 ± 2.5; Post: 14.5 ± 2.2; Detraining: 17.6 ± 2.2; p = 0.007 NK cell cytotoxicity: Ratio 8:1 G1 - Pre: 31.8 ± 5.0; Post: 22.6 ± 4.7; Detraining: 21.3 ± 4.3; G2 - Pre: 19.4 ± 4.0; Post: 9.7 ± 3.6; Detraining: 12.7 ± 5.4; p = 0.144 Ratio 4:1 G1 - Pre: 21.9 ± 4.0; Post: 17.5 ± 4.0; Detraining: 23.4 ± 2.3; G2 - Pre: 15.4 ± 3.1; Post: 13.0 ± 3.2; Detraining: 19.6 ± 5.9; p = 0.482 Ratio 2:1 G1 - Pre: 17.9 ± 3.9; Post: 14.0 ± 3.1; Detraining: 19.9 ± 2.7; G2 - Pre: 12.5 ± 2.4; Post: 11.2 ± 3.2; Detraining: 17.2 ± 5.0; p = 0.326 Ratio 1:1 G1 - Pre: 16.1 ± 4.0; Post: 11.1 ± 2.7; Detraining: 16.8 ± 2.7; G2 - Pre: 10.5 ± 1.3; Post: 10.5 ± 3.3; Detraining: 14.2 ± 4.7; p = 0.386	Leukocytes: Ø; p = 0.842 T cells (%): Ø; p = 0.611 B cells (%): Ø; p = 0.185 NK cells (%): Ø; p = 0.398 NK cell cytotoxicity: - Ratio 8:1 p = 0.038 - Ratio 4:1– p = 0.814 - Ratio 2:1 – p = 0.763 - Ratio 1:1 p = 0.717
Ashem et al., (2020)	Breast Cancer (stage 1)	18 weeks, 3x/wk G1: Aerobic exercises (treadmill, cycle ergometer, or elliptical machine). 1^st-6^th wks, 60%VO_2max; 7-12wk, 70% VO_2max; 12^th wk 80% VO_2max. 1^st-3^rd wks: 15min, increase 5min every 3 wk; 18^th wk – 45min G2: Usual Care	N: 30 women G1: 15 (45y) G2: 15 (45.06y)	CTx	Time points: Baseline End of intervention Collection methods: Phlebotomy	Immunoglobulins IgA G1 - Pre: 230.69 ± 7.33; Post: 255.74 ± 11.27; p = 0.0001 G2: Pre: 230.76 ± 7.31; Post: 225.38 ± 12.26; p = 0.112	Immunoglobulin IgA Pre: .98; Post: .0001
Ligibel et al. (2019)	Breast cancer	Meantime: 29.3 days G1: 60-90 min, 2x/wk; 30-45 min of at least moderate-intensity aerobic training; 20 min of resistance training; 10 min cool down and stretching. Total (supervised and unsupervised): 220 min/wk, 40 min of strength, and 180 min of MICT G2: Mind-body control	N: 48 (52y)/ 46 G1: 26 (52.3y)/ 25 G2: 22 (53.1y)/ 21	Scheduled for primary breast surgery	Time points: Baseline End of intervention Collection methods: Radioimmunoassay Automated chemistry analyzer ELISA		FOXP3⁺ cells G1 - Pre: 0.44 ± 0.53; Post: 0.76 ± 1.42; G2 - Pre: 0.45 ± 0.77; Post: 2.68 ± 3.57; p = 0.08 CD4+ G1 - Pre: 0.04 ± 0.05; Post: 36.57 ± 133.42; G2 - Pre: 0.36 ± 0.90; Post: 0.80 ± 0.82; p = 0.64 CD56+: Ø G1 - Pre: 1.86 ± 2.15; Post: 1.33 ± 2.34; p = G2 - Pre: 2.14 ± 3.94; Post: 0.90 ± 0.81; p = 0.53 CD8+ G1 - Pre: 1.36 ± 1.38; Post: 1.60 ± 2.51; G2 - Pre: 1.43 ± 1.13; Post: 1.44 ± 2.08; p = 0.89 CD163+ G1 - Pre: 5.85 ± 5.40; Post: 1.40 ± 1.32; G2 - Pre: 6.01 ± 7.85; Post: 1.14 ± 1.27; p = 0.85
Djurhuus et al. (2023)	Prostate cancer	2 to 8 weeks G1: 4x/wk; warm-up: 20-25 min of aerobic HIIT; stationary bicycle ergometer; 4-6 cycles of high-intensity intervals for 1 min at 100-120% Wpeak, followed by 3 min of active recovery at 30% Wpeak G2: Usual care	N: 30 G1: 20 (63y) G2: 10 (68y)	Undergoing radical prostatectomy	Time points: Baseline Follow up (before surgery) Collection methods: Immunohistochemical analysis	Tumour NK cells – G1 - Pre: 0.47 ± 0.48; Post: 2.07 ± 1.65; p = 0.004 G2 - Pre: 1.05 ± 1.37; Post: 1.49 ± 1.17; p = 0.396 Healthy NK cells – G1 - Pre: 0.62 ± 0.78; Post: 1.95 ± 1.48; p = 0.210 G2 - Pre: 4.15 ± 4.50; Post: 2.26 ± 1.59; p = 0.102	Tumour NK-cell infiltration: Ø (p = 0.114) NK-cell infiltration in the healthy prostatic tissue: G1 > G2 (p = 0.046)
Djurhuus et al. (2022)	Prostate cancer	Acute (one bout) G1: Peak power output (Wpeak) test followed by an HIIT bout; bicycle ergometer; warm-up 3 min at 70 W, increase of 20 W/min until exhaustion. 10 min active recovery at 30% of Wpeak; four HIIT cycles - 1 min at 100% Wpeak, and 3 min of active recovery at 30% of Wpeak. G2: Usual Care	N: 30 G1: 20 (64y) G2: 10 (65y)	Scheduled for radical prostatectomy	Time points: Baseline Immediately after the Wpeak test Immediately after the last HI 1h into the resting period Collection methods: Immunohistochemistry PT Link	Total blood lymphocyte count: G1 - Pre: 1.6 ± 0.4; Post-W_peak: 3.7 ± 1.0; Post-exercise: 3.4 ± 1.1; Post-1h rest: 1.3 ± 0.3; p (Pre vs Post-W_peak) < 0.001 p (Pre vs Post-exercise) < 0.001 p (Pre vs Post-1h rest) < 0.001	Tumor NK cell infiltration: Ø (p = 0.328)
Hojan, (2016)	Prostate cancer	8 weeks G1: 5x/wk MICT; 50-55 min: 30 min aerobic exercise (brisk walking, running indoors or on a treadmill, or cycling); 15 min resistance exercises, 2 sets of 8 reps at 70-75% RM G2: Usual care	N: 55 (68.5y) G1: 27 (67.4y) G2: 28 (69.9y)	Scheduled ADT	Time points: Baseline End of the intervention Collection methods: BD Cytometric Bead Array (CBA) Enhanced Sensitivity Flex Set Flow Cytometer	White blood cells G1 - Pre: 7.09 ± 1.70; Post: 5.35 ± 1.43; G2 - Pre: 7.61 ± 1.70; Post: 5.68 ± 1.68; Lymphocytes G1 - Pre: 1.84 ± 0.58; Post: 1.17 ± 0.94; G2 - Pre: 2.10 ± 0.58; Post: 1.11 ± 0.43; Platelets G1 - Pre: 218.00 ± 55.71; Post: 208.30 ± 40.20) G2 - Pre: 237.29 ± 39.58; Post: 211.79 ± 42.99;	Peripheral blood cell parameters: Ø
Rao et al. (2017)	Breast Cancer (stage IV)	12 wks G1: 60min, at least 2x/wk; integrated yoga-based stress: a set of asanas (postures done with awareness) breathing exercises, pranayama (voluntarily regulated nostril breathing), meditation, and yogic relaxation techniques with imagery reduction program. G2: Education and supportive therapy sessions	N: 91 (49.6y) G1: 45 (48.9y) G2: 46 (50.2y)	Undergoing radiotherapy	Time points: Baseline End of intervention Collection methods: Flow cytometer	NK cell % - G1 - Pre: 9.68 ± 4.28; Post: 11.32 ± 4.92; p < 0.01 G2 - Pre: 10.33 ± 5.61; Post: 8.73 ± 5.55; p = 0.32 Absolute lymphocyte count – G1 - Pre: 2016.05 ± 768.18; Post: 2041.26 ± 853.73 G2 - Pre: 1792.93 ± 997.22; Post: 1829.93 ± 797.73	NK cell % - G1 > G2: [F (1, 31) = 5.43, p = 0.03 Absolute lymphocyte count: Ø

NK cells, Natural killer cells; PBMCs, Peripheral blood mononuclear cells; Th1/Th2 ratio, CD3+ T lymphocyte subset helper cell type 1/CD3+ T lymphocyte subset helper cell type 2; NSCLC, non-small cells lung cancer; CTx, chemotherapy; TCR, T-cell receptor; RCT, randomized controlled trial.