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Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer
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Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer
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Journal Article
Intratumor Hypoxia Promotes Immune Tolerance by Inducing Regulatory T Cells via TGF-β1 in Gastric Cancer
2013
Overview
Regulatory T cell (Treg)-mediated immunosuppression represents one of the crucial tumor immune evasion mechanisms and is a main obstacle for successful tumor immunotherapy. Hypoxia, a common feature of solid tumors, has been associated with potentiated immunosuppression, decreased therapeutic response, malignant progression and local invasion. Unfortunately, the link between hypoxia and Treg-mediated immune tolerance in gastric cancer remains poorly understood. In our study, Tregs and hypoxia inducible factor-1α were found to be positively correlated with each other and were increased with the tumor progression. A subsequent in vitro study indicated that supernatants derived from gastric cancer cells under hypoxic condition, could induce the expression of Foxp3 via TGF-β1. These findings confirmed the crucial role of Tregs as a therapeutic target in gastric cancer therapy and provided helpful thoughts for the design of immunotherapy for gastric cancer in the future.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Aged
/ Biology
/ Cancer
/ Female
/ Forkhead Transcription Factors - metabolism
/ Humans
/ Hypoxia
/ Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
/ Male
/ Medicine
/ Stomach Neoplasms - immunology
/ Stomach Neoplasms - metabolism
/ Stomach Neoplasms - mortality
/ Stomach Neoplasms - pathology
/ T-Lymphocytes, Regulatory - immunology
/ T-Lymphocytes, Regulatory - metabolism
/ Transforming Growth Factor beta1 - metabolism
/ Transforming growth factor-b1
/ Tumors
