title: Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.
abstract: Progestagen-associated endometrial protein (PAEP) is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater) and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment.
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Chai
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China; Department of poisoning treatment, Beijing 307 hospital, Beijing, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Changlan
authors.initials: C
authors.lastname: Li
authors.affiliation: People's Hospital of Anqiu City, Anqiu, Shandong, China.
authors.forename: Qiquan
authors.initials: Q
authors.lastname: Ren
authors.affiliation: People's Hospital of Anqiu City, Anqiu, Shandong, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Yang
authors.affiliation: People's Hospital of Anqiu City, Anqiu, Shandong, China.
authors.forename: Fumei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Qiao
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Weijing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.affiliation: Advocate Christ Medical Center, Advocate Cancer Institute, Oak Lawn, IL, United States of America.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Riker
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Han
authors.affiliation: Department of Immunohematology, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Yu
mesh_terms: D045744:Cell Line, Tumor; D000071816:Glycodelin; D006023:Glycoproteins / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*
chemical_list: D000071816:Glycodelin; D006023:Glycoproteins; D007376:Interleukin-2; C045246:PAEP protein, human; D007371:Interferon-gamma