Cargando…

Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner

T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated thr...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Bokyoung, Lee, Jieun, Woo, Min-Yeong, Lee, Mi Jin, Shin, Ho-Joon, Kim, Kyongmin, Park, Sun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564046/
https://www.ncbi.nlm.nih.gov/pubmed/32932843
http://dx.doi.org/10.3390/microorganisms8091395
_version_ 1783595623728021504
author Lee, Bokyoung
Lee, Jieun
Woo, Min-Yeong
Lee, Mi Jin
Shin, Ho-Joon
Kim, Kyongmin
Park, Sun
author_facet Lee, Bokyoung
Lee, Jieun
Woo, Min-Yeong
Lee, Mi Jin
Shin, Ho-Joon
Kim, Kyongmin
Park, Sun
author_sort Lee, Bokyoung
collection PubMed
description T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. Bacterial gavage did not increase the alpha diversity of gut microbiota in antibiotic-treated mice but did alter the microbiome composition, which was associated with the restoration of the anti-tumour efficacy of Tim-3 blockade. Conclusively, our results indicate that gut microbiota modulation may improve the therapeutic efficacy of Tim-3 blockade during concomitant antibiotic treatment. The administered bacterial species and host factors should be considered in order to achieve therapeutically beneficial modulation of the microbiota.
format Online
Article
Text
id pubmed-7564046
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-75640462020-10-27 Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner Lee, Bokyoung Lee, Jieun Woo, Min-Yeong Lee, Mi Jin Shin, Ho-Joon Kim, Kyongmin Park, Sun Microorganisms Article T cell immunoglobulin and mucin domain-containing protein-3 (Tim-3) is an immune checkpoint molecule and a target for anti-cancer therapy. In this study, we examined whether gut microbiota manipulation altered the anti-tumour efficacy of Tim-3 blockade. The gut microbiota of mice was manipulated through the administration of antibiotics and oral gavage of bacteria. Alterations in the gut microbiome were analysed by 16S rRNA gene sequencing. Gut dysbiosis triggered by antibiotics attenuated the anti-tumour efficacy of Tim-3 blockade in both C57BL/6 and BALB/c mice. Anti-tumour efficacy was restored following oral gavage of faecal bacteria even as antibiotic administration continued. In the case of oral gavage of Enterococcus hirae or Lactobacillus johnsonii, transferred bacterial species and host mouse strain were critical determinants of the anti-tumour efficacy of Tim-3 blockade. Bacterial gavage did not increase the alpha diversity of gut microbiota in antibiotic-treated mice but did alter the microbiome composition, which was associated with the restoration of the anti-tumour efficacy of Tim-3 blockade. Conclusively, our results indicate that gut microbiota modulation may improve the therapeutic efficacy of Tim-3 blockade during concomitant antibiotic treatment. The administered bacterial species and host factors should be considered in order to achieve therapeutically beneficial modulation of the microbiota. MDPI 2020-09-11 /pmc/articles/PMC7564046/ /pubmed/32932843 http://dx.doi.org/10.3390/microorganisms8091395 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Bokyoung
Lee, Jieun
Woo, Min-Yeong
Lee, Mi Jin
Shin, Ho-Joon
Kim, Kyongmin
Park, Sun
Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title_full Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title_fullStr Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title_full_unstemmed Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title_short Modulation of the Gut Microbiota Alters the Tumour-Suppressive Efficacy of Tim-3 Pathway Blockade in a Bacterial Species- and Host Factor-Dependent Manner
title_sort modulation of the gut microbiota alters the tumour-suppressive efficacy of tim-3 pathway blockade in a bacterial species- and host factor-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564046/
https://www.ncbi.nlm.nih.gov/pubmed/32932843
http://dx.doi.org/10.3390/microorganisms8091395
work_keys_str_mv AT leebokyoung modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT leejieun modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT woominyeong modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT leemijin modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT shinhojoon modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT kimkyongmin modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner
AT parksun modulationofthegutmicrobiotaaltersthetumoursuppressiveefficacyoftim3pathwayblockadeinabacterialspeciesandhostfactordependentmanner