title: Tumor cell programmed death ligand 1-mediated T cell suppression is overcome by coexpression of CD80.
abstract: Programmed death ligand 1 (PDL1, or B7-H1) is expressed constitutively or is induced by IFN-γ on the cell surface of most human cancer cells and acts as a "molecular shield" by protecting tumor cells from T cell-mediated destruction. Using seven cell lines representing four histologically distinct solid tumors (lung adenocarcinoma, mammary carcinoma, cutaneous melanoma, and uveal melanoma), we demonstrate that transfection of human tumor cells with the gene encoding the costimulatory molecule CD80 prevents PDL1-mediated immune suppression by tumor cells and restores T cell activation. Mechanistically, CD80 mediates its effects through its extracellular domain, which blocks the cell surface expression of PDL1 but does not prevent intracellular expression of PDL1 protein. These studies demonstrate a new role for CD80 in facilitating antitumor immunity and suggest new therapeutic avenues for preventing tumor cell PDL1-induced immune suppression.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Haile
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: Bosch
authors.forename: Nnenna I
authors.initials: NI
authors.lastname: Agu
authors.forename: Annette M
authors.initials: AM
authors.lastname: Zeender
authors.forename: Preethi
authors.initials: P
authors.lastname: Somasundaram
authors.forename: Minu K
authors.initials: MK
authors.lastname: Srivastava
authors.forename: Sabine
authors.initials: S
authors.lastname: Britting
authors.forename: Julie B
authors.initials: JB
authors.lastname: Wolf
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Ksander
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ostrand-Rosenberg
mesh_terms: D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D060890:B7-H1 Antigen; D045744:Cell Line, Tumor; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C423236:CD274 protein, human