Abstract
A variety of pathogenic microorganisms promote tumor occurrence and development through long-term colonization in the body. Fusobacterium nucleatum (F. nucleatum) 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 regulatory T cell (Tregs) to allow tumor cells to escape immune surveillance and provide favorable conditions for their own long-term colonization. Tregs 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 F. nucleatum 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 F. nucleatum infection and Tregs infiltration. Therefore, we propose the view that chronic infection of F. nucleatum may provide favorable conditions for long-term colonization of itself by recruiting Tregs and suppressing the immune response. At the same time, the massive enrichment of Treg may also weaken the immune response and assist in the long-term colonization of F. nucleatum. We analyzed the correlation between F. nucleatum infection with the clinicopathological characteristics and survival prognosis of the patients. F. nucleatum 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 F. nucleatum infection are independent risk factors affecting ESCC prognosis. Additionally, the survival rate and median survival time were significantly shortened in the F. nucleatum 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 F. nucleatum infection. In turn, F. nucleatum infection and colonization may weaken the antitumor immune response through Treg enrichment and further assist in self-colonization, promoting the malignant progression of ESCC.
Highlights
Esophageal cancer has very high morbidity and mortality rates [1]
The mechanism of pathogenic microorganism infection in tumors is not completely clear, the removal of pathogenic microorganisms is helpful to control the malignant progression of tumors
The clinical stage and histological type were based on the 2017 Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM classification system for esophageal cancer
Summary
Esophageal cancer has very high morbidity and mortality rates [1]. There are approximately 500,000 new cases of esophageal cancer worldwide every year, more than half of which occur in China [2]. Squamous cell carcinoma is the most common histological type of esophageal cancer, accounting for more than 95% of all esophageal cancers. The prognosis of esophageal squamous cell carcinoma (ESCC) is extremely poor. Radiotherapy and chemotherapy, targeted therapy, and immunotherapy are constantly used in comprehensive tumor treatment, the 5 years survival rate of patients with advanced disease is still less than 20% [3]. The etiology of ESCC is not completely clear, and its risk factors include smoking, drinking, diet, chronic infection, immune dysfunction, and genetic susceptibility. The mechanism of pathogenic microorganism infection in tumors is not completely clear, the removal of pathogenic microorganisms is helpful to control the malignant progression of tumors
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