title: Relapse or eradication of cancer is predicted by peptide-major histocompatibility complex affinity.
abstract: Cancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro. We found that tumor eradication by T cells required high affinities of the targeted peptides for major histocompatibility complex (MHC) class I. Affinities of at least 10 nM were required for relapse-free regression. Only high-affinity peptide-MHC interactions led to efficient cross-presentation of antigen, thereby stimulating cognate T cells to secrete cytokines. These findings highlight the importance of targeting peptides with high affinity for MHC class I when designing T cell-based immunotherapy.
authors.affiliation: Department of Pathology, Committee on Immunology and Committee on Cancer Biology, The University of Chicago, Chicago, IL 60637, USA. bengels@bsd.uchicago.edu
authors.forename: Boris
authors.initials: B
authors.lastname: Engels
authors.forename: Victor H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: David C
authors.initials: DC
authors.lastname: Binder
authors.forename: Rebecca B
authors.initials: RB
authors.lastname: Liu
authors.forename: David M
authors.initials: DM
authors.lastname: Kranz
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Meredith
authors.forename: Donald A
authors.initials: DA
authors.lastname: Rowley
authors.forename: Hans
authors.initials: H
authors.lastname: Schreiber
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D045142:Cross-Priming; D015789:HLA-A2 Antigen / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D009842:Oligopeptides / Q000276:immunology; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D015789:HLA-A2 Antigen; D006681:HLA-D Antigens; D009842:Oligopeptides