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

作者：Seidel Ursula J E; Oliveira Claudia C; Lampen Margit H; van Hall Thorbald^*

来源：Cancer Immunology, Immunotherapy, 2012, 61(1): 119-125.

DOI：10.1007/s00262-011-1160-x

• T-cell epitopes associated with impaired peptide processing (TEIPP)
• Cytotoxic T lymphocytes (CTL)
• Tumor immune escape
• Antigen processing
• Transporter associated with peptide processing (TAP)
• CIMT2011

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.

• 出版日期2012-1