Relationship between <i>Fusobacterium nucleatum</i> and antitumor immunity in colorectal cancer liver metastasis

Sakamoto, Yuki; Mima, Kosuke; Ishimoto, Takatsugu; Ogata, Yoko; Imai, Katsunori; Miyamoto, Yuji; Akiyama, Takahiko; Daitoku, Nobuya; Hiyoshi, Yukiharu; Iwatsuki, Masaaki; Baba, Yoshifumi; Iwagami, Shiro; Yamashita, Yo‐ichi; Yoshida, Naoya; Komohara, Yoshihiro; Ogino, Shuji; Baba, Hideo

doi:10.1111/cas.15126

Cited by 35 publications

(26 citation statements)

References 38 publications

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“…In this study, we have elucidated that F. nucleatum administration promotes CRLM and is correlated with the activation of hepatic immune microenvironment. Interestingly, a recent study has innovatively demonstrated that F. nucleatum can be detected in liver metastases and the F. nucleatumpositive CRLM are associated with the reduced density of T cells [32]. Consistent with these findings, using in vivo murine models of CRC, we have shown that F. nucleatum reshapes the immune microenvironment in metastatic livers.…”

Section: Discussionsupporting

confidence: 88%

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota

Yin

Zhang

Wang

et al. 2022

Aging

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Liver metastasis is the major cause of death in colorectal cancer (CRC) patients. Nevertheless, the underlying mechanisms remain unknown. Gut microbiota intricately affect the initiation and progression of CRC by instigating immune response through the secretion of pro-inflammatory cytokines. In this study, we investigated the contribution of Fusobacterium nucleatum (F.nucleatum) to the microbiota-liver axis of CRC in mice, focusing on the correlation between liver immunity and gut microbiota alterations. When F. nucleatum was orally administered to mice, CRC liver metastasis was evidently exaggerated and accompanied by noticeable deleterious effects on body weight, cecum weight, and overall survival time. Further evaluation of the immune response and cytokine profiles revealed a substantial increase in the levels of pro-inflammatory cytokines such as IL6, IL12, IL9, IL17A, CXCL1, MCP-1, TNF-α, and IFN-γ in the plasma of mice treated with F. nucleatum as compared to that in the untreated control mice. Besides, hepatic immune response was also modulated by recruitment of myeloid-derived suppressor cells, reduction in the infiltration of natural killer (NK) and T helper-17 (Th17) cells, as well as increase in regulatory T cell accumulation in the liver. Additionally, sustained F. nucleatum exposure abridged the murine gut microbiota diversity, inducing an imbalanced and restructured intestinal microflora. In particular, the abundance of CRC-promoting bacteria such as Enterococcus and Escherichia/Shigella was evidently elevated post F. nucleatum treatment. Thus, our findings suggest that F. nucleatum might be an important factor involved in promoting CRC liver metastasis by triggering of liver immunity through the regulation of gut microbiota structure and composition.

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Section: Discussionsupporting

confidence: 88%

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota

Yin

Zhang

Wang

et al. 2022

Aging

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“…F. nucleatum induced a dramatic decrease in m 6 A modification in CRC cells and patient-derived xenograft tissues through downregulation of the m 6 A methyltransferase METTL3, resulting in CRC aggressiveness (95). A study quantified F. nucleatum DNA in 181 colorectal cancer liver metastasis (CRLM) specimens and found that F. nucleatumpositive CRLM showed a significantly lower density of CD8 + T cells and a higher density of MDSCs compared to F. nucleatumnegative CRLM, and the difference was statistically significant, but the relationship between F. nucleatum and density of tumorassociated macrophages (TAMs) was not statistically significant (96). F. nucleatum may be a biomarker of CRC (97).…”

Section: Colorectal Cancermentioning

confidence: 99%

The Role of The Tumor Microbiome in Tumor Development and Its Treatment

Chen

Wu²,

Wu³

et al. 2022

Front. Immunol.

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Commensal bacteria and other microorganisms that reside in the human body are closely associated with the development and treatment of cancers. Recently, tumor microbiome (TM) has been identified in a variety of cancers such as pancreatic, lung, and breast cancers. TM has different compositions in different tumors and has different effects on tumors. TM plays an important role in the formation of the tumor microenvironment, regulation of local immunity, and modification of tumor cell biology, and directly affects the efficacy of drug treatment for tumors. TM is expected to be a biomarker for tumors, and engineered tumor-targeting bacteria and anti-cancer microbial agents (GEN-001) have an important role in the treatment of tumors. This paper reviews the relevant studies on TM in recent years and describes its distribution in different tumors, its correlation with clinical features, its effect on local immunity, and the research directions of TM in tumor treatment.

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“…Meanwhile, cytokines (IL-10, IL-17) secreted by activated M2 macrophage, in turn, promote CRC cells invasion and metastasis by activating NF-κB pathway ( 79 ). Fusobacterium nucleatum can boost liver metastasis by modulating liver microenvironment featured with accumulation of MDSCs, and reduction of NK and Th17 cells ( 80 , 81 ). Peptostreptococcus anaerobius was also reported to induce chronic inflammation and modulate tumor microenvironment by recruiting MDSCs, TANs and TAMs ( 82 ).…”

Section: Gut Dysbiosis Facilitates Immune Escape In Crcmentioning

confidence: 99%

Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer

Hou

Zheng²,

Wei³

et al. 2022

Front. Immunol.

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Accumulating evidence suggests that gut microbial dysbiosis is implicated in colorectal cancer (CRC) initiation and progression through interaction with host immune system. Given the intimate relationship between the gut microbiota and the antitumor immune responses, the microbiota has proven to be effective targets in modulating immunotherapy responses of preclinical CRC models. However, the proposed putative mechanisms of how these bacteria affect immune responses and immunotherapy efficacy remains obscure. In this review, we summarize recent findings of clinical gut microbial dysbiosis in CRC patients, the reciprocal interactions between gut microbiota and the innate and/or the adaptive immune system, as well as the effect of gut microbiota on immunotherapy response in CRC. Increased understanding of the gut microbiota-immune system interactions will benefit the rational application of microbiota to the clinical promising biomarker or therapeutic strategy as a cancer immunotherapy adjuvant.

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Relationship between Fusobacterium nucleatum and antitumor immunity in colorectal cancer liver metastasis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution-NonCo mmercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 35 publications

References 38 publications

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota

Fusobacterium nucleatum promotes liver metastasis in colorectal cancer by regulating the hepatic immune niche and altering gut microbiota

The Role of The Tumor Microbiome in Tumor Development and Its Treatment

Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer

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