Exercise training to increase tumour natural killer‐cell infiltration in men with localised prostate cancer: a randomised controlled trial

Abstract

To explore the effects of preoperative high-intensity interval training (HIIT) compared to usual care on tumour natural killer (NK)-cell infiltration in men with localised prostate cancer (PCa), as NK-cell infiltration has been proposed as one of the key mechanisms whereby exercise can modulate human tumours. Patients and MethodsA total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four-times weekly (EX; n = 20) or usual care (CON; n = 10) from time of inclusion until scheduled surgery. Tumour NK-cell infiltration was assessed by immunohistochemistry (CD56 + ) in diagnostic core needle biopsies and corresponding prostatic tissue from the RP. Changes in cardiorespiratory fitness, body composition, blood biochemistry, and health-related quality of life were also evaluated. ResultsThe change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: À0.09 cells/mm 2 , 95% confidence interval [CI] -1.85 to 1.66; P = 0.913) in the intention-to-treat analysis. The total number of exercise sessions varied considerably from four to 30 sessions. The per-protocol analysis showed a significant increase in tumour NK-cell infiltration of 1.60 cells/mm 2 (95% CI 0.59 to 2.62; P = 0.004) in the EX group. Further, the total number of training sessions was positively correlated with the change in NK-cell infiltration (r = 0.526, P = 0.021), peak oxygen uptake (r = 0.514, P = 0.035) and peak power output (r = 0.506, P = 0.038). ConclusionPreoperative HIIT did not result in between-group differences in tumour NK-cell infiltration. Per-protocol and exploratory analyses demonstrate an enhanced NK-cell infiltration in PCa. Future studies are needed to test the capability of exercise to increase tumour immune cell infiltration.

The effects of acute exercise and inflammation on immune function in early-stage prostate cancer

“…Whether the observed effect of acute exercise on NKCA in the circulation translates to cancerous prostate tissue has not been investigated. In a recent study we found no difference in NK cell infiltration into tumor tissue in patients with early-stage prostate cancer randomized to exercise or control ( Djurhuus et al, 2022a , 2022b ). However, we found a positive correlation between the amount of high-intensity training sessions and NK cell infiltration into the tumor tissue indicating a potential dose-dependent relationship ( Djurhuus et al, 2022b ).…”

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer

“…From the findings that the acute exercise response in men with prostate cancer is normal, three implications for consideration regarding this type of physical activity are presented. (i) While a single exercise bout was insufficient ( 19 , 48 ), multiple sessions enhanced immune cell infiltration of prostate tumors ( 49 ) that aligns with data from pre-clinical models ( 50 , 51 ). (ii) Breast cancer cell culture experiments reveal that acute but not chronic exercise reduce cell viability ( 52 ), leading to the hypothesis that “every exercise bout matters” ( 53 ).…”

Molecular insights of exercise therapy in disease prevention and treatment

“… 227 However, these effects did not translate to humans, as indicated by two randomized controlled trials with prostate cancer patients. 228 , 229 Future studies will have to clarify if these mechanism translate to other tumor entities to elucidate the therapeutic significance of IL-6R signaling in exercise-induced immune cell trafficking.…”