Chapter 5 - Identification of tumor antigens for T-cell-mediated cancer immunotherapy

Abstract

Tumor cells always differ from normal somatic cells in the proteins or protein fragments that they contain. These can be presented to the immune system in the form of peptides bound to human leukocyte antigen (HLA) class I and/or HLA class II molecules. Provided that the tumor cells maintain expression of these major histocompatibility complex molecules at the cell surface, they remain potentially visible to the adaptive immune system. Even if the tumor cells downregulate HLA expression, it is still possible that neighboring antigen-presenting cells (APCs) acquire tumor antigens from dying tumor cells and can then also present these on their HLA molecules. In both cases, T cells are principally able to recognize such tumor peptides as HLA ligands and either destroy the tumor cells directly or influence tumor growth indirectly, for example, by cytokine secretion. The only unambiguous method for physically identifying the peptides actually presented on HLA by cancer cells or APC is mass spectrometry. HLA ligands identified as either tumor-specific or tumor-associated in such a way that T-cell responses targeting them are not harmful to the patient are valuable for different cancer immunotherapy strategies, in particular for vaccination or adoptive transfer of antigen-specific T cells. In all cases, these therapies have to be personalized since both types of expressed antigens vary from patient to patient and tumor to tumor.