| Autor: |
Seidel UJ; Department of Clinical Oncology, K1-P, Leiden University Medical Center, Albinusdreef 2, 2333 Leiden, The Netherlands., Oliveira CC, Lampen MH, Hall Tv |
| Jazyk: |
angličtina |
| Zdroj: |
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2012 Jan; Vol. 61 (1), pp. 119-25. Date of Electronic Publication: 2011 Nov 25. |
| DOI: |
10.1007/s00262-011-1160-x |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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