Your browser doesn't support javascript.
loading
Use of a novel microbiome modulator improves anticancer immunity in a murine model of malignant pleural mesothelioma.
Gattlen, Christophe; Frank, Kirby R; Marie, Damien N; Trompette, Aurélien; Chriqui, Louis-Emmanuel; Hao, Yameng; Abdelnour, Etienne; Gonzalez, Michel; Krueger, Thorsten; Dyson, Paul J; Siankevich, Sviatlana; von Garnier, Christophe; Ubags, Niki D J; Cavin, Sabrina; Perentes, Jean Y.
Afiliación
  • Gattlen C; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Frank KR; Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Marie DN; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Trompette A; Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Chriqui LE; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Hao Y; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Abdelnour E; Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
  • Gonzalez M; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Krueger T; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Dyson PJ; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Siankevich S; Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
  • von Garnier C; Embion Technologies SA, Etoy, Switzerland.
  • Ubags NDJ; Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Cavin S; Division of Pulmonology, Department of Medicine, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Perentes JY; Division of Thoracic Surgery, Department of Surgery, CHUV, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
JTCVS Open ; 18: 324-344, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38690424
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.
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: JTCVS Open / JTCVS open Año: 2024 Tipo del documento: Article País de afiliación: Suiza
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Idioma: En Revista: JTCVS Open / JTCVS open Año: 2024 Tipo del documento: Article País de afiliación: Suiza