Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice

Biochemical and Biophysical Research Communications
Chengming XuZifan Lu

Abstract

Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation.

Citations

Dec 7, 2017·Frontiers in Immunology·Kristian M Hargadon
Aug 30, 2018·International Journal of Cancer. Journal International Du Cancer·Kate R SecombeJoanne M Bowen
Dec 21, 2019·Breast Cancer Management·Alastair M McKeeStephen D Robinson
Mar 14, 2020·Scientific Reports·Michael A MalfattiGabriela G Loots
Sep 4, 2020·Cancers·Aurora Laborda-IllanesMaría Isabel Queipo-Ortuño
Jun 12, 2020·Cell Communication and Signaling : CCS·Zhujiang DaiDaorong Wang
May 1, 2021·Frontiers in Oncology·Wenyu LiTingtao Chen
May 12, 2021·Molecules and Cells·Jaeho Kim, Heung Kyu Lee

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