title: A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen.
abstract: NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8(+) T cell epitope, NY-ESO-1(88-96) (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1(157-165) epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1(88-96) is much more efficiently cross-presented from the soluble form, than NY-ESO-1(157-165). On the other hand, NY-ESO-1(157-165) is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A(26-35); whereas NY-ESO-1(88-96) was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1(88-96) is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18(+) melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1(88-96) from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8(+) T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne Austin Branch, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Rona Y
authors.initials: RY
authors.lastname: Zhao
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mifsud
authors.forename: Kun
authors.initials: K
authors.lastname: Xiao
authors.forename: Kok-Fei
authors.initials: KF
authors.lastname: Chan
authors.forename: Sara
authors.initials: S
authors.lastname: Oveissi
authors.forename: Heather M
authors.initials: HM
authors.lastname: Jackson
authors.forename: Nektaria
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Philippe
authors.initials: P
authors.lastname: Guillaume
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Knights
authors.forename: Tamara
authors.initials: T
authors.lastname: Lowen
authors.forename: Neil C
authors.initials: NC
authors.lastname: Robson
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Russell
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D059911:HLA-B18 Antigen / Q000276:immunology*; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000473:pathology
chemical_list: D000939:Epitopes; D059911:HLA-B18 Antigen