A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen

• Published in: PloS one 2012-09, Vol.7 (9), p.e44707-e44707
• Main Authors: Zhao, Rona Y, Mifsud, Nicole A, Xiao, Kun, Chan, Kok-Fei, Oveissi, Sara, Jackson, Heather M, Dimopoulos, Nektaria, Guillaume, Philippe, Knights, Ashley J, Lowen, Tamara, Robson, Neil C, Russell, Sarah E, Scotet, Emmanuel, Davis, Ian D, Maraskovsky, Eugene, Cebon, Jonathan, Luescher, Immanuel F, Chen, Weisan
• Format: Article
• Language: English
• Subjects: Antigen presentation; Antigenic determinants; Biology; Blotting, Western; Cancer vaccines; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Line, Tumor; Clinical trials; Comparative analysis; Dendritic cells; Dendritic Cells - immunology; Epitopes; Epitopes - immunology; Histocompatibility antigen HLA; HLA antigens; HLA-B18 Antigen - immunology; Humans; Immune response; Immunogenicity; Immunotherapy; Influenza; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Medicine; Melanoma; Melanoma - immunology; Melanoma - pathology; Patients; Peptides; Proteins; Skin cancer; T cell receptors; T cells; Tumor cell lines; Tumor cells; Tumors; Vaccines; Vaccinia virus; Viruses; Western blotting; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044707

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.