在之前报道的 I 期试验中，我们观察到前列腺癌 (PCa) 患者服用白蘑菇 (WBM) 片剂后，循环骨髓源性抑制细胞 (MDSC) 与治疗相关的下降。这些观察结果使我们假设 WBM 可以通过抑制 MDSC 来减缓 PCa 进展。我们进行了双向转化研究，以检查 WBM 消耗对同基因小鼠 PCa 模型和参与正在进行的随机 II 期试验 (NCT04519879) 的 PCa 患者的免疫调节作用在小鼠模型中，WBM 治疗可显着抑制肿瘤生长，同时减少 MDSC 的数量和功能，从而促进 T 细胞和自然杀伤 (NK) 细胞介导的抗肿瘤免疫反应。在患者中，服用 WBM 片剂 3 个月后，我们观察到循环多形核 MDSC (PMN-MDSC) 减少，同时细胞毒性 CD8 T 和 NK 细胞增加。此外，对 WBM 治疗患者外周血的单一免疫细胞分析显示，循环 PMN-MDSC 中 STAT3/IRF1 和 TGFβ 信号传导受到抑制。 PMN-MDSC 亚群呈现与真菌反应、中性粒细胞趋化性、白细胞聚集和炎症反应调节相关的转录谱。最后，在 PCa 小鼠模型中，我们发现 WBM 消耗增强了抗 PD-1 抗体的抗癌活性，表明 WBM 可用作免疫检查点抑制剂的辅助治疗。我们对 PCa 小鼠模型和患者的结果提供了机制深入了解 WBM 的免疫调节作用，并为 WBM 作为延缓或预防 PCa 进展的营养干预措施提供科学基础。白蘑菇 (WBM) 治疗导致促肿瘤 MDSC 减少，特别是多形核 MDSC (PMN-MDSC) ，同时激活抗肿瘤 T 细胞和 NK 细胞。人类单免疫细胞基因表达谱揭示了 WBM 诱导的分子改变，特别是 PMN-MDSC 上的分子改变。一项在小鼠模型中将 WBM 与 PD-1 阻断相结合的概念验证研究揭示了对肿瘤消退和生存结果的累加效应，强调了 WBM 在癌症管理中的临床相关性。© 2024 作者。约翰·威利出版的《临床与转化医学》

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.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).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+ T and NK cells. Furthermore, single immune cell profiling of peripheral blood from WBM-treated patients showed suppressed STAT3/IRF1 and TGFβ signalling in circulating PMN-MDSCs. Subclusters of PMN-MDSCs presented transcriptional profiles associated with responsiveness to fungi, neutrophil chemotaxis, leukocyte aggregation, and regulation of inflammatory response. Finally, in mouse models of PCa, we found that WBM consumption enhanced the anticancer activity of anti-PD-1 antibodies, indicating that WBM may be used as an adjuvant therapy with immune checkpoint inhibitors.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.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.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.