Journal
FUTURE ONCOLOGY
Volume 6, Issue 10, Pages 1577-1589Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/FON.10.128
Keywords
antigen-presenting machinery; antitumor immunotherapy; epigenetics; MHC class I expression; tumor vaccine
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Funding
- Grant Agency of the Czech Republic [301/07/1410, 301/10/2174]
- Grant Agency of the Academy of Sciences of the Czech Republic [IAA500520807, IAA500520605]
- Clinigene Network of Excellence for the Advancement of Gene Transfer and Therapy
- EU [018933]
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MHC class I downregulation is a general mechanism by which tumor cells can escape from T-cell-mediated immunity. This downregulation also represents a serious obstacle to the development of effective antitumor immunotherapy or vaccination. Therefore, successful immunotherapeutic and vaccination protocols should be optimized against tumors with distinct cell surface expression of the MHO class I molecules. Mechanisms leading to protective immunity may vary in different models with respect to the particular tumors (e.g., in their levels of residual expression of the MHC class I molecules on tumor cells or inducibility of MHC class I expression). Notably, both CD8+ cell-mediated immunity and MHC class I-unrestricted mechanisms can take place against MHC class I-deficient tumors. Since MHC class I downregulation is frequently reversible by cytokines and also by the activation of epigenetically silenced genes, an attractive strategy is to elicit specific cell-mediated immunity combined with restoration of MHC class I expression on tumor cells.
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