MHC/HLA Class-I Loss and Cancer Immune Escape

This chapter is about the progress made in the clinical application of tumour immunology. It describes the discovery of tumour antigens recognized by T lymphocytes as small peptides presented via HLA class-I molecules and the international effort that took place to immunize cancer patients with these tumour peptides in a “therapeutic vaccination”. I describe in detail the discovery of “cancer immune escape mechanisms” developed by tumour cells to avoid the immune destruction, in particular, the “loss of the HLA class-I molecules” in the cancer escape variants. The altered tumour HLA class-I phenotypes found in human tumours are included together with the responsible molecular mechanisms. It also analyses the clinical impact of the use of monoclonal antibodies involved in the regulation of T cell cytotoxicity: the “immune check-point” molecules. In 2018 Jim Allison (MD Anderson, Texas, USA) and Tasuku Honjo (University of Kyoto, Japan) were awarded with the Nobel Prize for these discoveries opening a new era in the immunotherapy of cancer.