Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Cell Line, Tumor
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Female
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Forkhead Transcription Factors / metabolism
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Humans
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Hypoxia*
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Immune Tolerance*
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Male
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Middle Aged
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Neoplasm Staging
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Stomach Neoplasms / immunology*
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Stomach Neoplasms / metabolism*
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Stomach Neoplasms / mortality
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Stomach Neoplasms / pathology
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Stomach Neoplasms / surgery
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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Transforming Growth Factor beta1 / metabolism*
Substances
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FOXP3 protein, human
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Forkhead Transcription Factors
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Hypoxia-Inducible Factor 1, alpha Subunit
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Transforming Growth Factor beta1
Grants and funding
This study was supported by the Shanghai Science and Technology Commission (10410709400, 10411950100), National Nature Science Foundation of China (81000968, 81101540, 81101637 and 81172273) and the National Clinical Key Special Subject of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.