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

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Kyungwon Lee¹  Hyukmin Lee¹  Jinseon Yoo²  Tae-Min Kim²  Hoguen Kim³  Byung Soh Min⁴  Eui-Cheol Shin⁵  Kyung-A Kim⁶  Won Kyu Kim⁷  Chang Gon Kim⁸  Sang Joon Shin⁸  Soonmyung Paik⁸  Joong Bae Ahn⁸  Han Sang Kim⁹ 

[1] Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea;Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea;Department of Surgery, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea;Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea;Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea;Natural Products Research Center, Korea Institute of Science and Technology, Gangneung, Republic of Korea;Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;Graduate School of Medical Science, Brain Korea 21 FOUR Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea;

关键词: anti-tumor immune response;    T cells;    gut microbiota;    Fusobacterium nucleatum;    colorectal cancer;   

DOI  :  10.3389/fcimb.2023.1101291

 received in 2022-11-17, accepted in 2023-02-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background & AimsFusobacterium 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.MethodsThe 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.ResultsGene 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.ConclusionFN 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.

【 授权许可】

Unknown   
Copyright © 2023 Kim, Kim, Kim, Kim, Yoo, Min, Paik, Shin, Lee, Lee, Kim, Shin, Kim and Ahn