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Figure 1: The baseline F. prausnitzii level is predictive of the response to anti-PD1. (A) Gopalakrishnan et al. Science 2017, (B) Spencer et al. Science 2.
Figure 2: FMT with microbiota from responders containing higher concentrations of F. prausnitzii, have a better ability to rescue efficacy in non-responders of anti-PD1. Gopalakrishnan et al. Science 2017.

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Faecalibacterium Prausnitzii IN IMMUNO-ONCOLOGY

Faecalibacterium prausnitzii (F. prau) to fight Cancer
A key intestinal bacterium associated with boosting effects on existing cancer treatments?

Recently, new hope has emerged that microbiota modulation might improve cancer treatments. Several teams around the world have demonstrated that Faecal Microbiota Transplants (FMT) could rescue efficacy in non-responders of immune checkpoint inhibitors in a series of clinical trials. Inspired by these promising results, but also conscious of the limits associated with this approach (reproducibility, scalability, cost), there is increasing interest in the development of more controlled microbiota-modulating therapies (1), of which F. prausnitzii would be the ideal candidate. It is a well characterised, extremely oxygen sensitive, commensal, immune-modulating bacteria that in responders of immunotherapies, abundantly colonises the gastro-intestinal tract. A series of published clinical observations have led us to make some assumptions around the potentiation immunotherapy properties of F. prausnitzii:

  • The F. prausnitzii level is predictive of the response to anti-PD1: low levels of F. prausnitzii are associated with a reduction in progression-free survival in patients with metastatic melanoma, treated with anti-PD1 (2) (Figure 1).
  • A high level of F. prausnitzii in the donor’s stool is associated with a better response rate to FMT in patients with melanoma: FMT with microbiota from responders that contain higher concentrations of F. prausnitzii, have a better chance to improve efficacy in non-responders of anti-PD1 (3, 4) (Figure 2).

F. prausnitzii seems to play a critical role in our ability to respond to immune-checkpoint inhibitors in the treatment of cancer.

Because they are lacking this bacterium, non-responding patients do not have a fair chance to improve their condition. Increasing the level of F. prausnitzii in patients, by administering an F. prausnitzii-based product, could potentially lead to longer, progression-free survival periods.

References:

  1. J. Erdmann. How gut bacteria could boost cancer treatments. Nature. News Feature, 19 July 2022.
  2. Gopalakrishnan V, Spencer C N, Nezi L, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 2018. Jan 5;359(6371):97-103.
  3. Davar D, Dzutsev A, McCulloch J, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 2021. Feb 5;371(6529):595-602.
  4. Spencer C, Mcquade J, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response. Science 2021. Dec 23; Vol 374, Issue 6575 pp. 1632-1640
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