Tumour MHC class I downregulation and immunotherapy (Review)
Jazyk angličtina Země Řecko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
PubMed
14534734
Knihovny.cz E-zdroje
- MeSH
- alely MeSH
- buňky NK cytologie MeSH
- CD8-pozitivní T-lymfocyty metabolismus MeSH
- down regulace * MeSH
- fenotyp MeSH
- haplotypy MeSH
- histokompatibilita - antigeny třídy I biosyntéza imunologie MeSH
- imunoterapie metody MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádory imunologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- histokompatibilita - antigeny třídy I MeSH
MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype. Altered MHC class I antigen expression involves total loss, loss of haplotype, locus downregulation, allelic loss or downregulation, and combinations. Description of partial or complete losses of MHC class I molecules in tumour cells as mechanisms of immune escape often fails to consider an increased susceptibility to NK cell-mediated lysis, which is a direct consequence of such losses. A low MHC class I level favours NK cells as effectors, whereas a high level of MHC class I favours T cells as effectors. The microheterogeneity of MHC class I expression in tumour cell populations, the balance of the MHC-restricted and MHC-unrestricted defence as well as the selective pressure of antigen-specific (CTL) and antigen non-specific (NK) effector mechanisms decide the final outcome of the MHC class I expression in the primary tumour and its metastases as well as the final outcome of the tumour defence reaction. Despite the MHC class I molecule deficiency and the resulting absence of the CD8+ T cell-mediated immunity, the tumour hosts were found to be capable of being immunized against MHC class I- tumours. The purpose of this review is to discuss the positive results of MHC class I- tumour treatment obtained with immunomodulatory cytokines and tumour vaccines, as well as the prospects and limitations of such therapy.