AUTHOR=Zhang Ning , Liu Yiwen , Yuan Xiang , Liang Mengxia , Wang Xiaopeng , Wang Min , Kong Jinyu , Yang Hong , Zhou Fuyou 

TITLE=Clinical Significance of Fusobacterium nucleatum Infection and Regulatory T Cell Enrichment in Esophageal Squamous Cell Carcinoma

JOURNAL=Pathology and Oncology Research

VOLUME=27

YEAR=2021

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2021.1609846

DOI=10.3389/pore.2021.1609846

ISSN=1532-2807

ABSTRACT=<p>A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. <italic>Fusobacterium nucleatum</italic> (<italic>F. nucleatum</italic>) is abundant in precancerous esophageal lesions and is closely related to the malignant progression of esophageal squamous cell carcinoma (ESCC). The invasion of exogenous microorganisms can reshape the immune microenvironment, make the immune system incapacitated, and assist tumor cells in immune escape. A variety of pathogenic microorganisms induce the recruitment of <italic>regulatory T cell</italic> (<italic>Tregs</italic>) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. <italic>Tregs</italic> are one of the major obstacles to tumor immunotherapy and have a significant positive correlation with the occurrence and development of many kinds of tumors. Because <italic>F. nucleatum</italic> can instantly enter cells and colonize for a long time, we speculated that F. nucleatum infection could facilitate the immune escape of tumor cells through enrichment of Tregs and promote the malignant progression of ESCC. In this study, we found a significant concordance between <italic>F. nucleatum</italic> infection and <italic>Tregs</italic> infiltration. Therefore, we propose the view that chronic infection of <italic>F. nucleatum</italic> may provide favorable conditions for long-term colonization of itself by recruiting <italic>Tregs</italic> and suppressing the immune response. At the same time, the massive enrichment of <italic>Treg</italic> may also weaken the immune response and assist in the long-term colonization of <italic>F. nucleatum</italic>. We analyzed the correlation between <italic>F. nucleatum</italic> infection with the clinicopathological characteristics and survival prognosis of the patients. <italic>F. nucleatum</italic> infection was found to be closely related to sex, smoking, drinking, degree of differentiation, depth of invasion, lymph node metastasis, and clinical stage. The degree of differentiation, depth of infiltration, lymph node metastasis, clinical stage, and <italic>F. nucleatum</italic> infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the <italic>F. nucleatum</italic> infection positive group. Therefore, we propose that long-term smoking and alcohol consumption cause poor oral and esophageal environments, thereby significantly increasing the risk of <italic>F. nucleatum</italic> infection. In turn, <italic>F. nucleatum</italic> infection and colonization may weaken the antitumor immune response through <italic>Treg</italic> enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.</p>