Microbiome et santé humaine : avancées technologiques

Microbiome et santé humaine : avancées technologiques pour de nouvelles perspectives
Impact of Gut Microbiota on the Efficacy of Anticancer Treatments
Présenté par Bertrand Routy (MD) - Institut Gustave Roussy U1015 - Villejuif
ABSTRACT
Inhibition of immune regulatory checkpoints, such as CTLA-4 and PD-1/PDL-1 are at the
forefront of cancer treatment. The limits of these monoclonal antibodies (mAb) are the
unpredictable efficacy and the immune related toxicities. Our team demonstrated that
intestinal commensals were part of the answer; specific mucosal dysbiosis could dictate
sensitivity or resistance to immune checkpoint inhibitors. We worked on the first-in-class
immune checkpoint blocker (ICB), anti-CTLA-4 mAb/ipilimumab, and showed the mandatory
role of microbiota (Bacteroidales and Burkholderiales) in its antitumor immune effects and the
prophylactic role of such commensals against subclinical colitis in mice (Vétizou M, Science
2015). In parallel, another group demonstrated the importance of Bifidobacterium in maturing
intratumoral dendritic cells that allow the expansion of anti-cancer T cells in the tumor beds
and their activation with anti-PDL-1 mAb. (Sivan A, Science 2015)
We developed in collaboration with Institut National de la Recherche en Agroalimentaire a
novel diagnosis tool based on metagenomic signatures of the feces of more than 100 lung and
renal cell cancer patients, to predict response/resistance to PD1 inhibitor (Nivolumab). To
confirm this signature, we performed fecal microbial transplantation from patients’ feces in
germ free mice.
Furthermore, for patients’ feces lacking the most immunogenic bacteria and being resistant
to PD1, in our germ free model bacterial compensation restored the activity of PD1.
Our objective is to provide adjuvant compensatory therapies based on administration of
Oncobax i.e. live commensal bacteria to promote clinical responses.
KEY WORDS
Immune checkpoint inhibitors, lung cancer, kidney cancer