Immunoprotecting Effects of Exercise Program against Ovarian Cancer: A Single-Blind, Randomized Controlled Trial

Abstract

Exercise is known to help the immune function of cancer survivors after cancer cell removal, but there is little information about the effect of exercise on ovarian cancer survivors. We conducted this study to investigate the effects of exercise training on the physical fitness and innate immunity of ovarian cancer survivors (OCS). Twenty-seven OCS between forty-two and sixty-one years of age volunteered for this study. The participants were divided into a control group (COG, n = 15) and an exercise group (EXG, n = 12). The mean (SD) age was 51.07 (5.67) years, and the mean post-operation period was 45.96 (5.88) months. EXG participated in regular exercise training 6 days a week for 12 weeks. Body weight, fat mass, and body mass index of EXE were significantly decreased compared with those of COG. The muscle mass in EXE was increased compared to that of COG. Physical fitness factors showed positive changes in EXG compared to COG. We found that exercise training enhanced lymphocyte and neutrophil counts of leucocytes and total natural killer (NK) and natural killer T (NKT) cell counts of lymphocytes through improved body composition and physical fitness after 12 weeks. Moreover, we found that improved innate immune cells through the exercise program were achieved through an increase in NKG₂D+NK receptors and a decrease in KIR₂DL₃+NK receptors in OCS.

Keywords: NK cell receptors; NK cells; muscle mass; ovarian cancer; regular exercise.

Figure 1

Participants’ allocation (consolidated standards for reporting of trials flow diagram).

Figure 2

Flow cytometry analysis of NK cells in an ovarian cancer-removed survivor. A front scattered light (FSC)-A and side scattered light (SSC)-A plot were used to identify nucleated cells. (A) A lymphocyte gate was set based on the size and granularity of the cells. (B) Single cells were gated, and doublets were excluded. (C) CD14+ macrophages were excluded. (D) NK cells were defined as CD3−CD56+. (E) Two NK cell subsets were identified: CD16+ and CD16− NK cells. NKG2D and KIR2DL3 were defined as CD314 and CD158b, respectively.

Figure 3

Aerobic exercise + resistance exercise for 6 days a week of 12 weeks improves the physical fitness of survivors after ovarian cancer resection. (A) Peak oxygen consumption (VO₂ peak) in the control group (COG) and in the exercise group (EXG). (B) Flexibility in the COG and EXG. (C) Strength in the COG and EXG. (D) Muscle endurance in the COG and EXG. (E) Percentages of VO₂ peak analyzed as Δ% in both groups. (F) Percentages of flexibility analyzed as Δ% in both groups. (G) Percentages of strength analyzed as Δ% in both groups. (H) Percentages of muscle endurance analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (H), these tests were performed independently at each time point; ^### p < 0.001. p-values were calculated by Student’s t test or Wilcoxon signed rank test. For (A) to (D), these tests were performed dependently at each time point; * p < 0.05 and ** p < 0.01.

Figure 4

Body composition is improved in the ovarian cancer survivors after 12 weeks of aerobic and resistance exercise. (A) Body weight in the control group (COG) and in the exercise group (EXG). (B) Fat mass in the COG and EXG. (C) Body mass index in the COG and EXG. (D) Muscle mass in the COG and EXG. (E) Percentages of body weight analyzed as Δ% in both groups. (F) Percentages of fat mass analyzed as Δ% in both groups. (G) Percentages of body mass index analyzed as Δ% in both groups. (H) Percentages of muscle mass analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (H), these tests were performed independently at each time point; ns: not significance; ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001. p-values were calculated by Student’s t test or Wilcoxon signed rank test. For (A) to (D), these tests were performed dependently at each time point; * p < 0.05.

Figure 5

Neutrophils and lymphocytes of leucocytes are improved in the ovarian cancer survivors after 12 weeks of aerobic and resistance exercise. (A) Leucocyte’s absolute values in the control group (COG) and in the exercise group (EXG). (B) Neutrophil percentages of leucocyte’s absolute values in the COG and EXG. (C) Lymphocyte percentages of leucocyte’s absolute values in the COG and EXG. (D) Percentages of leucocyte analyzed as Δ% in both groups. (E) Percentages of neutrophil analyzed as Δ% in both groups. (F) Percentages of lymphocyte analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (F), these tests were performed independently at each time point; ns: not significance; ^## p < 0.01, and ^### p < 0.001. p-values were calculated by Student’s t test or Wilcoxon signed rank test. For (A) to (C), these tests were performed dependently at each time point; * p < 0.05 and ** p < 0.01.

Figure 6

NK and NKT cells of lymphocytes are improved in the ovarian cancer survivors after 12 weeks of aerobic and resistance exercise. (A) Lymphocyte’s absolute values in the control group (COG) and in the exercise group (EXG). (B) NK cell percentages of lymphocyte’s absolute values in the COG and EXG. (C) NKT cell percentages of lymphocyte’s absolute values in the COG and EXG. (D) Percentages of lymphocyte analyzed as Δ% in both groups. (E) Percentages of NK cells analyzed as Δ% in both groups. (F) Percentages of NKT cells analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (F), these tests were performed independently at each time point; ^# p < 0.05, ^## p < 0.01, and ^### p < 0.001. p-values were calculated by Student’s t test or Wilcoxon signed rank test. For (A) to (C), these tests were performed dependently at each time point; ns: p > 0.05 and ** p < 0.01.

Figure 7

NKG₂D+NK and KIR₂DL₃+NK receptors of total NK cells are improved in the ovarian cancer survivors after 12 weeks of aerobic and resistance exercise. (A) Total NK cells’ absolute values in the control group (COG) and in the exercise group (EXG). (B) NKG₂D+NK receptor percentages of total NK cells’ absolute values in the COG and EXG. (C) KIR₂DL₃+NK receptor percentages of total NK cells’ absolute values in the COG and EXG. (D) Percentages of total NK cells analyzed as Δ% in both groups. (E) Percentages of NKG₂D+NK receptor analyzed as Δ% in both groups. (F) Percentages of KIR₂DL₃+NK receptor analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (F), these tests were performed independently at each time point; ^## p < 0.01 and ^### p < 0.001. p-values were calculated by Student’s t test or Wilcoxon signed rank test. For (A) to (C), these tests were performed dependently at each time point; ns: p > 0.05, * p < 0.05, ** p < 0.01, and *** p < 0.001.

Figure 8

Cytotoxicity increases in the ovarian cancer survivors after 12 weeks of aerobic and resistance exercise. (A) Cytotoxic values in the control group (COG) and in the exercise group (EXG). (B) Percentages of cytotoxicity analyzed as Δ% in both groups. All data are represented as means ± SD. p-values were calculated by Student’s t test or Mann–Whitney U test. For (A) to (B), these tests were performed independently at each time point; ^### p < 0.001. p-values were calculated by Wilcoxon signed rank test. For (A), the test was performed dependently at each time point; ** p < 0.01.