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Dynamic switch of immunity and antitumor effects of metformin in rat spontaneous esophageal carcinogenesis
- Source :
- Cancer Immunology, Immunotherapy. 71:777-789
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Chronic inflammation contributes to tumor development by creating a local microenvironment that facilitates neoplastic transformation and potentiates the progression of cancer. Esophageal cancer (EC) is an inflammation-associated malignancy with a poor prognosis. The nature of the switch between chronic inflammation of the esophagus and EC-related immunological changes remains unclear. Here, we examined the dynamic alterations of immune cells at different stages of chronic esophagitis, Barrett’s esophagus (BE) and EC using an esophageal spontaneous carcinogenesis rat model. We also investigated the anticancer effects of metformin. To stimulate EC carcinogenesis, chronic gastroduodenal reflux esophagitis via esophagojejunostomy was induced in 120 rats in metformin-treated and non-treated (control) groups. After 40 weeks, BE and EC developed in 96.7% and 63.3% of the control group, and in 66.7% and 23.3% of the metformin-treated group, respectively. Flow cytometric analysis demonstrated that the balance of M1/M2-polarized or phospho-Stat3-positive macrophages, regulatory T, cytotoxic T, natural killer (NK), NK T cells, and Th17 T cells was dynamically changed at each stage of the disease and were resolved by metformin treatment. These findings clarify the immunity in esophageal carcinogenesis and suggest that metformin could suppress this disease by improving the immunosuppressive tumor microenvironment and immune evasion.
- Subjects :
- Cancer Research
Esophageal Neoplasms
Carcinogenesis
Immunology
Adenocarcinoma
medicine.disease_cause
Barrett Esophagus
Immune system
Tumor Microenvironment
medicine
Animals
Immunology and Allergy
Cytotoxic T cell
Neoplastic transformation
Reflux esophagitis
Tumor microenvironment
business.industry
Chronic Esophagitis
Esophageal cancer
medicine.disease
Metformin
Rats
Oncology
Cancer research
business
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....b3141a89c1f2039a7e6b4c0a8459bdd2