Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesotheliomaCentral MessagePerspective

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

JTCVS Open (Apr 2024)

Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesotheliomaCentral MessagePerspective

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

Affiliations

Christophe Gattlen, PhD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Kirby R. Frank, MSc: Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Damien N. Marie, MSc: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Aurélien Trompette, MSc: Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Louis-Emmanuel Chriqui, MD, PhD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Yameng Hao, PhD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
Etienne Abdelnour, MD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Michel Gonzalez, MD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Thorsten Krueger, MD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Paul J. Dyson, PhD: Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
Sviatlana Siankevich, PhD: Embion Technologies SA, Etoy, Switzerland
Christophe von Garnier, MD: Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Niki D.J. Ubags, PhD: Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Sabrina Cavin, PhD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
Jean Y. Perentes, MD, PhD: Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Address for reprints: Jean Y. Perentes, MD, PhD, Division of Thoracic Surgery, Lausanne University Hospital (CHUV), Rue du Bugnon 46, Lausanne, 1011, Switzerland.

Journal volume & issue: Vol. 18
pp. 324 – 344

Abstract

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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.

Published in JTCVS Open

ISSN: 2666-2736 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system; Medicine: Surgery
Website: https://www.journals.elsevier.com/jtcvs-open

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