title: Mechanisms regulating enhanced human leukocyte antigen class II-mediated CD4 + T cell recognition of human B-cell lymphoma by resveratrol.
abstract: Malignant B-cells express measurable levels of human leukocyte antigen (HLA) class II proteins, but often escape immune recognition by CD4 + T cells. Resveratrol (Resv) has been the focus of numerous investigations due to its potential chemopreventive and anti-cancer effects, but it has never been tested in the regulation of immune components in B-cell tumors. Here, we show for the first time that Resv treatment enhances HLA class II-mediated immune detection of B-cell lymphomas by altering immune components and class II presentation in tumor cells. Resv treatment induced an up-regulation of both classical and non-classical HLA class II proteins (DR and DM) in B-lymphoma cells. Resv also altered endolysosomal cathepsins (Cat S, B and D) and a thiol reductase (GILT), increasing HLA class II-mediated antigen (Ag) processing in B-cell lymphomas and their subsequent recognition by CD4 + T cells. Mechanistic study demonstrated that Resv treatment activated the recycling class II pathway of Ag presentation through up-regulation of Rab 4B protein expression in B-lymphoma cells. These findings suggest that HLA class II-mediated immune recognition of malignant B-cells can be improved by Resv treatment, thus encouraging its potential use in chemoimmunotherapy of B-cell lymphoma.
authors.affiliation: Department of Microbiology and Immunology, Hollings Cancer Center and Children's Research Institute, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Faisal F Y
authors.initials: FF
authors.lastname: Radwan
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhang
authors.forename: Azim
authors.initials: A
authors.lastname: Hossain
authors.forename: Bently P
authors.initials: BP
authors.lastname: Doonan
authors.forename: Jason M
authors.initials: JM
authors.lastname: God
authors.forename: Azizul
authors.initials: A
authors.lastname: Haque
mesh_terms: D017951:Antigen Presentation; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002403:Cathepsins / Q000378:metabolism; D049109:Cell Proliferation; D004705:Endocytosis; D005434:Flow Cytometry; D006681:HLA-D Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006681:HLA-D Antigens; D013267:Stilbenes; D002403:Cathepsins; D000077185:Resveratrol