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

By A. Sivan, L. Corrales, N. Hubert, Jason B. Williams, K. Aquino-Michaels, Z. Earley, Franco W. Benyamin, Y. Lei, B. Jabri, M. Alegre and 2 more. Science, 2015

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Gut microbes affect immunotherapy The unleashing of antitumor T cell responses has ushered in a new era of cancer treatment. Although these therapies can cause dramatic tumor regressions in some patients, many patients inexplicably see no benefit. Mice have been used in two studies to investigate what might be happening. Specific members of the gut microbiota influence the efficacy of this type of immunotherapy (see the Perspective by Snyder et al.). Vétizou et al. found that optimal responses to anticytotoxic T lymphocyte antigen blockade required specific Bacteroides spp. Similarly, Sivan et al. discovered that Bifidobacterium spp. enhanced the efficacy of antiprogrammed cell death ligand 1 therapy. Science, this issue, p. 1079 and p. 1084; see also p. 1031 Gut microbes modulate the effectiveness of cancer immunotherapies in mice. [Also see Perspective by Snyder et al.] 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.

Subfields: Epidemiology, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/514e52838f7513a8eab75a51814d2d06acca1baf

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Citations in the corpus

Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018, background): “Importantly, the administration of these bacteria also added to the therapeutic effect of anti-PD-1 treatment in these mice (125).”
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Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy (2017, background): “Recent mouse studies have shown that the gut microbiota may modulate local immune responses and in turn affect chemotherapy (Iida et al., 2013; Viaud et al., 2013) and immunotherapy (Sivan et al., 2015; Vétizou et al., 2015).”
Human Gut Microbiota and Gastrointestinal Cancer (2018, background): “Moreover, tumor progression is almost prohibited after the treatment [234].”
Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3 (2020, background): “ Bifidobacterium breve and other Bifidobacterium spp have been shown to encode amylopullulanases and attach to starch particles, and they have also been reported for their potential protective role against carcinogenesis here and previously (Sivan et al., 2015) .”
Organoid modeling of the tumor immune microenvironment (2018, background): “The stable transduction of the B16-SIYmelanoma line with the immunogenic SIYRYYGL peptide (SIY) allows FACS enumeration of organoid CD8 TILs bearing SIY-reactive TCR via SIY peptide-loaded H-2K tetramer staining (Sivan et al., 2015).”
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