title: Analysis of CD8+ Treg cells in patients with ovarian cancer: a possible mechanism for immune impairment.
abstract: Regulatory T (Treg) cells may participate in mediating a suppressive microenvironment that blunts successful anti-tumor immunotherapy. Recent studies show that CD8(+) Treg cells might impede effective immune responses to established tumors. However, there is limited research regarding CD8(+) Treg cells in ovarian cancer (OC) patients. Here, we investigated CD8(+) Treg cells in OC patients and their in vitro induction. The immunohistochemistry of tumor-infiltrating lymphocytes revealed a significant correlation between the intratumoral CD8(+) T cells and the forkhead box p3 (Foxp3)(+) cells in the intraepithelial and stromal areas of advanced OC tissues. We examined the expression of Treg markers in CD8(+) T cells from the peripheral blood and fresh tumor tissues of OC patients using flow cytometry. Our results indicated an increase in the CD8(+) Treg cell subsets of OC patients compared with those in patients with benign ovarian tumors and healthy controls, including an increased expression of CD25, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and Foxp3 and decreased CD28 expression. To demonstrate whether the tumor microenvironment could convert CD8(+) effector T cells into suppressor cells, we used an in vitro transwell culturing system. Compared with the CD8(+) T cells cultured alone, the CD8(+) Treg cells induced in vitro by coculture with SK-OV-3/A2780 showed increased CTLA-4 and Foxp3 expression and decreased CD28 expression. In addition, the in vitro-induced CD8(+) Treg cells inhibited naı¨ve CD4(+) T-cell proliferation, which was partially mediated through TGF-β1 and IFN-γ. Our study suggests that CD8(+) Treg cells were increased in OC patients and could be induced in vitro, which may be the way that tumors limit antitumor immunity and evade immune surveillance.
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Ke
authors.affiliation: Department of Obstetrics and Gynecology, Southwest Hospital, Third Military Medical University, Chongqing, China.|Department of Obstetrics and Gynecology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors.forename: Suyun
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Jianfang
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Peijun
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.|National Key Clinical Department of Laboratory Medicine, Nanjing, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Pan
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1