title: A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens.
abstract: Deficiencies in MHC class I antigen presentation are a common feature of tumors and allows escape from cytotoxic T lymphocyte (CTL)-mediated killing. It is crucial to take this capacity of tumors into account for the development of T-cell-based immunotherapy, as it may strongly impair their effectiveness. A variety of escape mechanisms has been described thus far, but progress in counteracting them is poor. Here we review a novel strategy to target malignancies with defects in the antigenic processing machinery (APM). The concept is based on a unique category of CD8+ T-cell epitopes that is associated with impaired peptide processing, which we named TEIPP. We characterized this alternative peptide repertoire emerging in MHC-I on tumors lacking classical antigen processing due to defects in the peptide transporter TAP (transporter associated with peptide processing). These TEIPPs exemplify interesting parallels with the folktale figure Cinderella: they are oppressed and neglected by a stepmother (like functional TAP prevents TEIPP presentation), until the suppression is released and Cinderella/TEIPP achieves unexpected recognition. TEIPP-specific CTLs and their cognate peptide-epitopes provide a new strategy to counteract immune evasion by APM defects and bear potential to targeting escape variants observed in a wide range of cancers.
authors: Department of Clinical Oncology, K1-P, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The Netherlands.
authors: Ursula J E
authors: UJ
authors: Seidel
authors: Claudia C
authors: CC
authors: Oliveira
authors: Margit H
authors: MH
authors: Lampen
authors: Thorbald van
authors: Tv
authors: Hall
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019139:Tumor Escape / Q000276:immunology
chemical_list: D018528:ATP-Binding Cassette Transporters; D018984:Epitopes, T-Lymphocyte; C477327:transporter associated with antigen processing (TAP)