Christophe Gattlen PhD , Kirby R. Frank MSc , Damien N. Marie MSc , Aurélien Trompette MSc , Louis-Emmanuel Chriqui MD, PhD , Yameng Hao PhD , Etienne Abdelnour MD , Michel Gonzalez MD , Thorsten Krueger MD , Paul J. Dyson PhD , Sviatlana Siankevich PhD , Christophe von Garnier MD , Niki D.J. Ubags PhD , Sabrina Cavin PhD , Jean Y. Perentes MD, PhD
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引用次数: 0
Abstract
Objective
Malignant pleural mesothelioma is a fatal disease and a clinical challenge, as few effective treatment modalities are available. Previous evidence links the gut microbiome to the host immunoreactivity to tumors. We thus evaluated the impact of a novel microbiome modulator compound (MMC) on the gut microbiota composition, tumor immune microenvironment, and cancer control in a model of malignant pleural mesothelioma.
Methods
Age- and weight-matched immunocompetent (n = 23) or athymic BALB/c mice (n = 15) were randomly assigned to MMC or no treatment (control) groups. MMC (31 ppm) was administered through the drinking water 14 days before AB12 malignant mesothelioma cell inoculation into the pleural cavity. The impact of MMC on tumor growth, animal survival, tumor-infiltrating leucocytes, gut microbiome, and fecal metabolome was evaluated and compared with those of control animals.
Results
The MMC delayed tumor growth and significantly prolonged the survival of immunocompetent animals (P = .0015) but not that of athymic mice. The improved tumor control in immunocompetent mice correlated with increased infiltration of CD3+CD8+GRZB+ cytotoxic T lymphocytes in tumors. Gut microbiota analyses indicated an enrichment in producers of short chain fatty acids in MMC-treated animals. Finally, we observed a positive correlation between the level of fecal short chain fatty acids and abundance of tumor-infiltrating cytotoxic T cells in malignant pleural mesothelioma.
Conclusions
MMC administration boosts antitumor immunity, which correlates with a change in gut microbiome and metabolome. MMC may represent a valuable treatment option to combine with immunotherapy in patients with cancer.