Reduction of myeloid-derived suppressor cells in prostate cancer murine models and patients following white button mushroom treatment.

Publication Title

Clin Transl Med

Document Type

Article

Publication Date

10-1-2024

Keywords

Animals; Male; Myeloid-Derived Suppressor Cells; Prostatic Neoplasms; Mice; Humans; Disease Models, Animal; Agaricales; Mice, Inbred C57BL; clinical trial; myeloid‐derived suppressor cells (MDSCs); nutraceutical intervention; prostate cancer; single immune cell profiling; white button mushroom.; california; santa monica; sjci

Abstract

BACKGROUND: In a previously reported Phase I trial, we observed therapy-associated declines in circulating myeloid-derived suppressor cells (MDSCs) with the administration of white button mushroom (WBM) tablets in prostate cancer (PCa) patients. These observations led us to hypothesise that WBM could mitigate PCa progression by suppressing MDSCs.

METHODS: We performed bidirectional translational research to examine the immunomodulatory effects of WBM consumption in both syngeneic murine PCa models and patients with PCa participating in an ongoing randomised Phase II trial (NCT04519879).

RESULTS: In murine models, WBM treatment significantly suppressed tumour growth with a reduction in both the number and function of MDSCs, which in turn promoted antitumour immune responses mediated by T cells and natural killer (NK) cells. In patients, after consumption of WBM tablets for 3 months, we observed a decline in circulating polymorphonuclear MDSCs (PMN-MDSCs), along with an increase in cytotoxic CD8

CONCLUSION: Our results from PCa murine models and patients provide mechanistic insights into the immunomodulatory effects of WBM and provide a scientific foundation for WBM as a nutraceutical intervention to delay or prevent PCa progression.

HIGHLIGHTS: White button mushroom (WBM) treatment resulted in a reduction in pro-tumoural MDSCs, notably polymorphonuclear MDSCs (PMN-MDSCs), along with activation of anti-tumoural T and NK cells. Human single immune cell gene expression profiling shed light on the molecular alterations induced by WBM, specifically on PMN-MDSCs. A proof-of-concept study combining WBM with PD-1 blockade in murine models revealed an additive effect on tumour regression and survival outcomes, highlighting the clinical relevance of WBM in cancer management.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Pharmacy

DOI

10.1002/ctm2.70048

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