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Fusobacterium nucleatum induces a tumor microenvironment with diminished adaptive immunity against colorectal cancers

Authors
 Han Sang Kim  ;  Chang Gon Kim  ;  Won Kyu Kim  ;  Kyung-A Kim  ;  Jinseon Yoo  ;  Byung Soh Min  ;  Soonmyung Paik  ;  Sang Joon Shin  ;  Hyukmin Lee  ;  Kyungwon Lee  ;  Hoguen Kim  ;  Eui-Cheol Shin  ;  Tae-Min Kim  ;  Joong Bae Ahn 
Citation
 FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol.13(1101291), 2023-03 
Journal Title
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
Issue Date
2023-03
Abstract
Background & Aims: Fusobacterium nucleatum (FN) plays a pivotal role in the development and progression of colorectal cancer by modulating antitumor immune responses. However, the impact of FN on immune regulation in the tumor microenvironment has not been fully elucidated.

Methods: The abundance of FN was measured in 99 stage III CRC tumor tissues using quantitative polymerase chain reaction. Gene expression profiles were assessed and annotated using consensus molecular subtypes (CMS), Gene Ontology (GO) analysis, and deconvolution of individual immune cell types in the context of FN abundance. Immune profiling for tumor infiltrating T cells isolated from human tumor tissues was analyzed using flow cytometry. Ex vivo tumor-infiltrating T cells were stimulated in the presence or absence of FN to determine the direct effects of FN on immune cell phenotypes.

Results: Gene expression profiles, CMS composition, abundance of immune cell subtypes, and survival outcomes differed depending on FN infection. We found that FN infection was associated with poorer disease-free survival and overall survival in stage III CRC patients. FN infection was associated with T cell depletion and enrichment of exhausted CD8+ and FoxP3+ regulatory T cells in the tumor microenvironment. The presence of FN in tumors was correlated with a suppressive tumor microenvironment in a T cell-dependent manner.

Conclusion: FN enhanced the suppressive immune microenvironment with high depletion of CD8+ T cells and enrichment of FoxP3+ regulatory T cells in human colorectal cancer cases. Our findings suggest a potential association for FN in adaptive immunity, with biological and prognostic implications.
Files in This Item:
T202301571.pdf Download
DOI
10.3389/fcimb.2023.1101291
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chang Gon(김창곤)
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
Kim, Hogeun(김호근)
Min, Byung Soh(민병소) ORCID logo https://orcid.org/0000-0003-0180-8565
Paik, Soon Myung(백순명) ORCID logo https://orcid.org/0000-0001-9688-6480
Shin, Sang Joon(신상준) ORCID logo https://orcid.org/0000-0001-5350-7241
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
Lee, Hyuk Min(이혁민) ORCID logo https://orcid.org/0000-0002-8523-4126
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193669
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