Dataset Information

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

ABSTRACT:

Objectives

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 methods

A 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.

Results

The change in tumour NK-cell infiltration did not differ between the EX and CON groups (between-group difference: -0.09 cells/mm² , 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/mm² (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).

Conclusion

Preoperative 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.

SUBMITTER: Djurhuus SS

PROVIDER: S-EPMC10084118 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Djurhuus Sissal Sigmundsdóttir SS Simonsen Casper C Toft Birgitte Grønkaer BG Thomsen Simon Nørskov SN Wielsøe Sabrina S Røder Martin Andreas MA Hasselager Thomas T Østergren Peter Busch PB Jakobsen Henrik H Pedersen Bente Klarlund BK Hojman Pernille P Brasso Klaus K Christensen Jesper Frank JF

BJU international 20220718 1

<h4>Objectives</h4>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.<h4>Patients and methods</h4>A total of 30 patients with localised PCa undergoing radical prostatectomy (RP) were randomised (2:1) to either preoperative aerobic HIIT four ...[more]

PMID: 35753072

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Project description:BackgroundNatural killer (NK) cells are non-antigen specific innate immune cells that can be redirected to targets of interest using multiple strategies, although none are currently FDA-approved. We sought to evaluate NK cell infiltration into tumors to develop an improved understanding of which histologies may be most amenable to NK cell-based therapies currently in the developmental pipeline.MethodsDNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from tumors from 45 cancer types (N = 90,916 for all cancers and N = 3365 for prostate cancer) submitted to Caris Life Sciences. NK cell fractions and immune deconvolution were inferred from RNA-seq data using quanTIseq. Real-world overall survival (OS) and treatment status was determined and Kaplan-Meier estimates were calculated. Statistical significance was determined using X2 and Mann-Whitney U tests, with corrections for multiple comparisons where appropriate.ResultsIn both a pan-tumor and prostate cancer (PCa) -specific setting, we demonstrated that NK cells represent a substantial proportion of the total cellular infiltrate (median range 2-9% for all tumors). Higher NK cell infiltration was associated with improved OS in 28 of 45 cancer types, including (PCa). NK cell infiltration was negatively correlated with common driver mutations and androgen receptor variants (AR-V7) in primary prostate biopsies, while positively correlated with negative immune regulators. Higher levels of NK cell infiltration were associated with patterns consistent with a compensatory anti-inflammatory response.ConclusionsUsing the largest available dataset to date, we demonstrated that NK cells infiltrate a broad range of tumors, including both primary and metastatic PCa. NK cell infiltration is associated with improved PCa patient outcomes. This study demonstrates that NK cells are capable of trafficking to both primary and metastatic PCa and are a viable option for immunotherapy approaches moving forward. Future development of strategies to enhance tumor-infiltrating NK cell-mediated cytolytic activity and activation while limiting inhibitory pathways will be key.

Dataset Information

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

Objectives

Patients and methods

Results

Conclusion

Publications

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

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