A novel category of antigens enabling CTL immunity to tumor escape variants: Cinderella antigens

Cancer Immunol Immunother. 2012 Jan;61(1):119-25. doi: 10.1007/s00262-011-1160-x. Epub 2011 Nov 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / immunology*
  • Animals
  • Antigen Presentation
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunotherapy
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Escape / immunology

Substances

  • ATP-Binding Cassette Transporters
  • Epitopes, T-Lymphocyte
  • transporter associated with antigen processing (TAP)