Folia Biologica
Journal of Cellular and Molecular Biology, Charles University 

Most of recent human immunotherapy stategies are based on the activation of MHC class I-restricted mechanisms such as CD8⁺ cytotoxic T lymphocytes (CTLs). However, malignant conversion of mammalian cells followed by immune selection in tumour cell populations is frequently associated with the loss of function of MHC class I genes which were expressed in malignant cell precursors. The MHC class I downregulation results in decreased sensitivity of the tumour cells to MHC class I-restricted CTLs, the major component of the tumour rejection reaction. Due to cross-priming by MHC class I⁻ donors’ dendritic cells, which can use their own MHC class I molecules for antigen presentation, in the peripheral blood of MHC class I⁻ tumour patients, the CD8⁺ CTLs can be detected (Offringa et al., 2000). However, these CTLs cannot attack the MHC class I⁻ tumour cells and this can provide the explanation for the paradoxical detection of CTLs in the peripheral blood of vaccinated patients in spite of the absence of any clinical responses. Thus, the MHC class I restriction of the CD8⁺ T cellmediated immunity can provide the MHC class I⁻ tumours with a possibility to escape from immune surveillance. Therefore, the MHC class I status of the tumour to be treated by immunotherapeutic or immunomodulatory gene therapy strategies should be established prior to the decision which therapeutic protocol is suitable for the respective tumour patient. Unfortunately, this requirement is usually not respected and this may be one reason why in the majority of clinical tumour immunotherapy trials the complete and partial responses have been found to be rather rare.

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