MHC/HLA Class I Loss in Cancer Cells.

In this chapter I describe Tumour Immune Escape mechanisms associated with MHC/HLA class I loss in human and experimental tumours. Different altered HLA class-I phenotypes can be observed that are produced by different molecular mechanisms. Experimental and histological evidences are summarized indicating that at the early stages of tumour development there is an enormous variety of tumour clones with different MHC class I expression patterns. This phase is followed by a strong T cell mediated immune-selection of MHC/HLA class-I negative tumour cells in the primary tumour lesion. This transition period results in a formation of a tumour composed only of HLA-class I negative cells. An updated description of this process observed in a large variety of human tumors is included. In the second section I focus on MHC/HLA class I alterations observed in mouse and human metastases, and describe the generation of different tumor cell clones with altered MHC class I phenotypes, which could be similar or different from the original tumor clone. The biological and immunological relevance of these observations is discussed. Finally, the interesting phenomenon of metastatic dormancy is analyzed in association with a particular MHC class I negative tumor phenotype.