Immune-refractory cancers and their little helpers—An extended role for immunetolerogenic MHC molecules HLA-G and HLA-E?

There is strong evidence to support a role for non-classical MHC class I (class Ib) molecules, most notably HLA-E and HLA-G in tumour immune escape. In this article, we summarize the current knowledge on their expression, regulation and functional relevance in various malignancies, particularly brain tumours. Special emphasis is devoted to the phenomenon that these tolerogenic molecules are expressed by non-transformed cells that are found in close neighborhood to tumour cells representing either parenchymal cells or immune cells attracted to the tumour microenvironment. Here they may act as “natural” or “inducible” suppressors of anti-tumoural immune responses. We thus speculate about the role of HLA-G expressing T cells, a novel population of natural regulatory cells that was identified recently. It is suggested that various cell types within a tumour cooperate in order to inhibit anti-tumour immunity—and that immunetolerogenic HLA-G may play a major role in this context.