Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jul 1;13(1):2374954.
doi: 10.1080/2162402X.2024.2374954. eCollection 2024.

Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors

Marius Bredon  1   2 , Camille Danne  1   2 , Hang Phuong Pham  3 , Pauline Ruffié  4 , Alban Bessede  5 , Nathalie Rolhion  1   2 , Laura Creusot  1   2 , Loic Brot  1   2 , Iria Alonso  1   2 , Philippe Langella  6 , Lisa Derosa  7   8   9 , Alexis B Cortot  10 , Bertrand Routy  11   12 , Laurence Zitvogel  7   8   9   13 , Nicola Segata  14   15 , Harry Sokol  1   2   6
Affiliations

Faecalibaterium prausnitzii strain EXL01 boosts efficacy of immune checkpoint inhibitors

Marius Bredon et al. Oncoimmunology. .

Abstract

Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of Faecalibacterium prausnitzii have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of F. prausnitzii at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of F. prausnitzii strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. F. prausnitzii strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.

Keywords: Cancer; gut microbiota; immune checkpoint inhibitor.

PubMed Disclaimer

Conflict of interest statement

HS report lecture fee, board membership, or consultancy from Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, Biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, Abbvie, has stocks from Enterome bioscience and is co-founder of Exeliom Biosciences. PL report lecture fee, board membership, or consultancy from Biose, Biostime, Boiron, Bonduelle, BMS, Bromatech, IPSEN, iTaK, Lallemand, Lesaffre, L’Oréal, Mayoli, Merck, Procter and Gamble, Second Genome, Therascience and URGO and is co-founder of Exeliom Biosciences. PR is an employee of Exeliom Biosciences. LD was supported by Philantropia Fondation. BR reports grants from Davoltera outside the submitted work, as well as consulting fees from BMS, AstraZeneca, Merck and Davolterra and he is the co-founder of Curebiota. ABC reports lecture fee, board membership, or consultancy from Amgen, Astra-Zeneca, Novartis, Merck KGaA, Pfizer, Roche, Janssen, Abbvie, Sanofi, Takeda, MSD, BMS, InhaTarget and Exeliom. The other authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
F. prausnitzii level predicts clinical response to PD-L1 in patients with advanced non-small-cell lung cancer.
Figure 2.
Figure 2.
F. prausnitzii level predicts clinical response to ICI in a dominant group of patients with advanced melanoma.
Figure 3.
Figure 3.
F. prausnitzii EXL01strain restores anti-tumor response to ICI in presence of ABX-induced gut microbiota perturbation.
Figure 4.
Figure 4.
F. prausnitzii EXL01 strain administration does not impact fecal microbiota composition and diversity.
Figure 5.
Figure 5.
F. prausnitzii EXL01strain administration restores normal response to ICI at the tumor transcriptomics level in gut microbiota perturbation context.
Figure 6.
Figure 6.
F. prausnitzii EXL01 boost activation of dendritic cells and T cells in the presence of anti-PD-L1.
See this image and copyright information in PMC

References

    1. Ribas A, Wolchok JD.. Cancer immunotherapy using checkpoint blockade. Science. 2018;359(6382):1350–12. doi:10.1126/science.aar4060. - DOI - PMC - PubMed
    1. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–97. doi:10.1126/science.aan3706. - DOI - PubMed
    1. Derosa L, Hellmann MD, Spaziano M, Halpenny D, Fidelle M, Rizvi H, Long N, Plodkowski AJ, Arbour KC, Chaft JE, et al. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. Annals of Oncology. 2018;29(6):1437–1444. doi:10.1093/annonc/mdy103. - DOI - PMC - PubMed
    1. Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, Boselli L, Routier E, Cassard L, Collins M, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28(6):1368–1379. doi:10.1093/annonc/mdx108. - DOI - PubMed
    1. Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, Frenkel EP, Koh AY.. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. Neoplasia. 2017;19(10):848–855. doi:10.1016/j.neo.2017.08.004. - DOI - PMC - PubMed

MeSH terms

Substances