Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy

Abstract

T cell infiltration of solid tumors is associated with favorable patient outcomes, yet the mechanisms underlying variable immune responses between individuals are not well understood. One possible modulator could be the intestinal microbiota. We compared melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, which were eliminated upon cohousing or after fecal transfer. Sequencing of the 16S ribosomal RNA identified Bifidobacterium as associated with the antitumor effects. Oral administration of Bifidobacterium alone improved tumor control to the same degree as programmed cell death protein 1 ligand 1 (PD-L1)–specific antibody therapy (checkpoint blockade), and combination treatment nearly abolished tumor outgrowth. Augmented dendritic cell function leading to enhanced CD8+ T cell priming and accumulation in the tumor microenvironment mediated the effect. Our data suggest that manipulating the microbiota may modulate cancer immunotherapy.

Is autoimmunity the Achilles' heel of cancer immunotherapy?

“…Similarly, it was reported that Bifidobacterium spp. enhanced the efficacy of anti-PD-L1 therapy 84 . It is possible that interindividual differences in the microbiome account for substantial heterogeneity in therapeutic efficacy and the immunopathology that is invoked after checkpoint blockade 85 .…”

Impact of environmental factors on alloimmunity and transplant fate

“…Although administration of probiotics may seem like adding "a drop in the bucket," feeding of Bifidobacterium species in mice that lacked this genus was recently shown to allow establishment of these species in the gut and improve antitumor immunity in a mouse model of melanoma (155). In transplantation, administration of probiotics reduced liver damage in rats following IRI (156) or liver transplantation and correlated with increased intestinal Tregs (157).…”

Microbiote intestinal et réponses aux thérapies anti-tumorales

“…Une équipe américaine a également attribué, dans la même édition du journal, un rôle à la flore intestinale dans l'efficacité du blocage impliquant une autre checkpoint blocker, l'axe PD1/PDL1 (programmed cell death ligand 1). Dans cette étude [34], le contrôle naturel de la croissance d'un mélanome implanté en sous-cutané a été comparé chez des animaux de fond génétique identique (C57Bl/6) mais provenant de fournisseurs différents (ce qui influe sur la colonisation des animaux en fonction de l'environnement qu'ils rencontrent au cours de l'élevage). Ils ont constaté que les animaux provenant des laboratoires Jackson (JAX) bénéficient d'un meilleur contrôle tumoral …”