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Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12
Mireia Uribe-Herranz, … , Carl H. June, Andrea Facciabene
Mireia Uribe-Herranz, … , Carl H. June, Andrea Facciabene
Published February 22, 2018
Citation Information: JCI Insight. 2018;3(4):e94952. https://doi.org/10.1172/jci.insight.94952.
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Research Article Immunology Microbiology

Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12

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Abstract

Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12–dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.

Authors

Mireia Uribe-Herranz, Kyle Bittinger, Stavros Rafail, Sonia Guedan, Stefano Pierini, Ceylan Tanes, Alex Ganetsky, Mark A. Morgan, Saar Gill, Janos L. Tanyi, Frederic D. Bushman, Carl H. June, Andrea Facciabene

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Figure 1

The gut microbiota influences effectiveness of adoptive cell therapy.

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The gut microbiota influences effectiveness of adoptive cell therapy.
(A...
(A) Impact of ACT on tumor growth in mice obtained from Jackson and Harlan. Means ± SEM are shown. Differences in tumor volume were evaluated with linear mixed effects models. ***P < 0.001. (B) Principal coordinates analysis (PCoA) of bacterial community composition, using unweighted UniFrac distance. (C) Bacterial taxa observed in Jackson and Harlan mice at 7 days and 21 days following ACT.

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