title: Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-β1 in gastric cancer.
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.
authors.affiliation: Department of Gastroenterology, Second Clinical School of Yangzhou University, Yangzhou, Jiangsu, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Deng
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Liu
authors.forename: Yan-Bing
authors.initials: YB
authors.lastname: Ding
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Xiao
authors.forename: Guo-Tao
authors.initials: GT
authors.lastname: Lu
authors.forename: Ping
authors.initials: P
authors.lastname: Bo
authors.forename: Xi-Zhong
authors.initials: XZ
authors.lastname: Shen
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007108:Immune Tolerance; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D053773:Transforming Growth Factor beta1