@Article{or.2025.072661,
AUTHOR = {Ke Liu, Xia Xue, Haiming Qin, Jiaying Zhu, Meng Jin, Die Dai, Youcai Tang, Ihtisham Bukhari, Hangfan Liu, Chunjing Qiu, Feifei Ren, Pengyuan Zheng, Yang Mi, Weihua Chen},
TITLE = {Gut Associated Metabolites Enhance PD-L1 Blockade Efficacy in Prostate Cancer},
JOURNAL = {Oncology Research},
VOLUME = {34},
YEAR = {2026},
NUMBER = {2},
PAGES = {0--0},
URL = {http://www.techscience.com/or/v34n2/65591},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> The gut microbiome has emerged as a critical modulator of cancer immunotherapy response. However, the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer (PC) remain not fully explored. The study aimed to explore how gut metabolites regulate death-ligand 1 (PD-L1) blockade via exosomes and boost immune checkpoint inhibitors (ICIs) in PC. <b>Methods:</b> We recruited 70 PC patients to set up into five subgroups. The integrated multi-omics analysis was performed. In parallel, we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate (TRAMP) models. <b>Results:</b> We identified two metabolites, 16(R)-Hydroxyeicosatetraenoic acid (16(R)-HETE) and 6-Keto-Prostaglandin E1 (6-Keto-PGE1), that positively correlated with the plasma exosomal PD-L1 levels. The <i>in vitro</i> experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA, protein, and exosome levels in both human and mouse PC cell lines, which were also validated <i>in vivo</i> based on subcutaneous mouse models. Both metabolites significantly promoted the anti-PD-L1 efficacy against PC <i>in situ</i> on a TRAMP mouse model. <b>Conclusions:</b> Targeting the “gut-tumor metabolic axis” is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.},
DOI = {10.32604/or.2025.072661}
}