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

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TLDR
Comparison of melanoma growth in mice harboring distinct commensal microbiota and observed differences in spontaneous antitumor immunity, suggests that manipulating the microbiota may modulate cancer immunotherapy.
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.

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Citations
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Journal ArticleDOI

Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

Bertrand Routy, +76 more
- 05 Jan 2018 - 
TL;DR: It is found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition, and Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer.
Journal ArticleDOI

Elements of cancer immunity and the cancer–immune set point

Daniel S. Chen, +1 more
- 19 Jan 2017 - 
TL;DR: Clinical studies are beginning to define these factors as immune profiles that can predict responses to immunotherapy, suggesting that a broader view of cancer immunity is required.
Journal ArticleDOI

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
Journal ArticleDOI

Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

TL;DR: Examination of the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients.
References
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Journal ArticleDOI

Naïve Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy

TL;DR: The RDP Classifier can rapidly and accurately classify bacterial 16S rRNA sequences into the new higher-order taxonomy proposed in Bergey's Taxonomic Outline of the Prokaryotes, and the majority of the classification errors appear to be due to anomalies in the current taxonomies.
Journal ArticleDOI

UniFrac: a New Phylogenetic Method for Comparing Microbial Communities

TL;DR: The results illustrate that UniFrac provides a new way of characterizing microbial communities, using the wealth of environmental rRNA sequences, and allows quantitative insight into the factors that underlie the distribution of lineages among environments.
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